4299 lines
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Entry
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- *603968 - POLYMERASE, DNA, ETA; POLH
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- OMIM
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<p>
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<span class="h4">*603968</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/603968">Table View</a>
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000170734;t=ENST00000372236" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=5429" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603968" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000170734;t=ENST00000372236" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001291969,NM_001291970,NM_006502,XM_047418900" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_006502" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603968" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=04913&isoform_id=04913_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/POLH" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/5138988,5457144,5729982,11463971,16041729,34732732,59798441,119624614,119624615,119624616,119624617,193783756,193785802,194377454,221045690,233770153,634743304,634743306,2217361823,2313707790,2462608971" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q9Y253" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=5429" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000170734;t=ENST00000372236" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=POLH" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=POLH" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+5429" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/POLH" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:5429" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/5429" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr6&hgg_gene=ENST00000372236.9&hgg_start=43576185&hgg_end=43620523&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:9181" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:9181" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/polh" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603968[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603968[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/POLH/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000170734" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=POLH" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=POLH" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=POLH" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=POLH&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA279" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:9181" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0037141.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1891457" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/POLH#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:1891457" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/5429/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=5429" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00018721;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060421-4949" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5429" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=POLH&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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603968
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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POLYMERASE, DNA, ETA; POLH
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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RAD30, S. CEREVISIAE, HOMOLOG OF, A; RAD30A
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=POLH" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">POLH</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/6/530?start=-3&limit=10&highlight=530">6p21.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:43576185-43620523&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">6:43,576,185-43,620,523</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/6/530?start=-3&limit=10&highlight=530">
|
|
6p21.1
|
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</a>
|
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</span>
|
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</td>
|
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|
|
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<td>
|
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<span class="mim-font">
|
|
Xeroderma pigmentosum, variant type
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/278750"> 278750 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/603968" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603968" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<p>Using an improved cell-free assay for translesion DNA synthesis, <a href="#12" class="mim-tip-reference" title="Masutani, C., Araki, M., Yamada, A., Kusumoto, R., Nogimori, T., Maekawa, T., Iwai, S., Hanaoka, F. <strong>Xeroderma pigmentosum variant (XP-V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity.</strong> EMBO J. 18: 3491-3501, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369688</a>] [<a href="https://doi.org/10.1093/emboj/18.12.3491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369688">Masutani et al. (1999)</a> isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in xeroderma pigmentosum variant (XPV; <a href="/entry/278750">278750</a>) cell extracts. <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> demonstrated that this polymerase, symbolized POLH, is a human homolog of the yeast Rad30 protein identified as DNA polymerase eta (<a href="#9" class="mim-tip-reference" title="Johnson, R. E., Prakash, S., Prakash, L. <strong>Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Pol-eta.</strong> Science 283: 1001-1004, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9974380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9974380</a>] [<a href="https://doi.org/10.1126/science.283.5404.1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9974380">Johnson et al., 1999</a>). POLH and yeast Rad30 are members of a family of damage-bypass replication proteins which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. The XPV cDNA encodes a protein of 713 amino acids with a calculated molecular mass of 78.4 kD. The amino acid sequences of the human POLH and yeast Rad30 proteins are 19% identical and 31.9% similar. <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> found that POLH shares 7 conserved domains with other proteins of S. pombe, Arabidopsis thaliana, C. elegans, and S. cerevisiae. No known DNA polymerase motifs were identified in DNA polymerase eta. Northern blot analysis of RNAs from 5 XPV cell lines revealed 2 with major decreases in band intensity. Recombinant human DNA polymerase eta corrected the inability of XPV cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10385124+9974380+10369688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> independently cloned the human DNA polymerase eta gene, which they called hRAD30, by homology cloning of S. cerevisiae RAD30. DNA polymerase eta is involved in the error-free bypass of ultraviolet light damage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Oxidative damage to DNA had been proposed to have a role in cancer and aging. Oxygen-free radicals formed during normal aerobic cellular metabolism attack bases in DNA, and a 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the adducts formed. Eukaryotic replicative DNA polymerases replicate DNA containing 8-oxoG by inserting an adenine opposite the lesion; consequently, 8-oxoG is highly mutagenic and causes G:C to T:A transversions. Genetic studies in yeast have indicated a role for mismatch repair in minimizing the incidence of these mutations. The gene RAD30 of S. cerevisiae encodes a DNA polymerase, Pol-eta, that efficiently replicates DNA containing a cis-syn thymine-thymine dimer by inserting 2 adenines across from the dimer. <a href="#6" class="mim-tip-reference" title="Haracska, L., Yu, S.-L., Johnson, R. E., Prakash, L., Prakash, S. <strong>Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta.</strong> Nature Genet. 25: 458-461, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10932195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10932195</a>] [<a href="https://doi.org/10.1038/78169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10932195">Haracska et al. (2000)</a> showed that yeast and human POL-eta replicate DNA containing 8-oxoG efficiently and accurately by inserting a cytosine across from the lesion and by proficiently extending from this basepair. Consistent with these biochemical studies, a synergistic increase in the rate of spontaneous mutations occurs in the absence of POL-eta in the yeast ogg1 (<a href="/entry/601982">601982</a>) deletion mutant. <a href="#6" class="mim-tip-reference" title="Haracska, L., Yu, S.-L., Johnson, R. E., Prakash, L., Prakash, S. <strong>Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta.</strong> Nature Genet. 25: 458-461, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10932195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10932195</a>] [<a href="https://doi.org/10.1038/78169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10932195">Haracska et al. (2000)</a> stated that their results suggested an additional role for POL-eta in the prevention of internal cancers in humans that would otherwise result from the mutagenic replication of 8-oxoG in DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10932195" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F., Kunkel, T. A. <strong>Low fidelity DNA synthesis by human DNA polymerase-eta.</strong> Nature 404: 1011-1013, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10801132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10801132</a>] [<a href="https://doi.org/10.1038/35010014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10801132">Matsuda et al. (2000)</a> demonstrated that human POLH copies undamaged DNA with much lower fidelity than any other template-dependent DNA polymerase studied. POLH lacks an intrinsic proofreading exonuclease activity and, depending on the mismatch, makes 1 base substitution error for every 18 to 380 nucleotides synthesized. This very low fidelity indicates a relaxed requirement for correct basepairing geometry and indicates that the function of POLH may be tightly controlled to prevent potentially mutagenic DNA synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10801132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To overcome the catastrophic consequences associated with the demise of stalled replication forks, translesional synthesis polymerases promote DNA synthesis past lesions. Alternatively, a stalled fork may collapse and undergo repair by homologous recombination. <a href="#15" class="mim-tip-reference" title="McIlwraith, M. J., Vaisman, A., Liu, Y., Fanning, E., Woodgate, R., West, S. C. <strong>Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination.</strong> Molec. Cell 20: 783-792, 2005. Note: Erratum: Molec. Cell 21: 445 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16337601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16337601</a>] [<a href="https://doi.org/10.1016/j.molcel.2005.10.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16337601">McIlwraith et al. (2005)</a> found that human POLH extended DNA synthesis past lesions following formation of a D-loop structure, with the invading strand serving as primer. POLH showed highest specificity for the D loop and weaker association with replication forks and single- and double-stranded DNA. POLH interacted with the recombinase RAD51 (<a href="/entry/179617">179617</a>) in HeLa cells following DNA damage, and RAD51 stimulated the DNA extension activity of POLH. Extracts from an XPV cell line exhibited severely reduced D-loop extension activity. <a href="#15" class="mim-tip-reference" title="McIlwraith, M. J., Vaisman, A., Liu, Y., Fanning, E., Woodgate, R., West, S. C. <strong>Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination.</strong> Molec. Cell 20: 783-792, 2005. Note: Erratum: Molec. Cell 21: 445 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16337601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16337601</a>] [<a href="https://doi.org/10.1016/j.molcel.2005.10.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16337601">McIlwraith et al. (2005)</a> concluded that POLH promotes translesional synthesis at stalled replication forks and reinitiates DNA synthesis by homologous recombination repair. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16337601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>B lymphocytes diversify their immunoglobulin-variable (IgV) genes through homologous recombination-mediated Ig gene conversion. <a href="#10" class="mim-tip-reference" title="Kawamoto, T., Araki, K., Sonoda, E., Yamashita, Y. M., Harada, K., Kikuchi, K., Masutani, C., Hanaoka, F., Nozaki, K., Hashimoto, N., Takeda, S. <strong>Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis.</strong> Molec. Cell 20: 793-799, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16337602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16337602</a>] [<a href="https://doi.org/10.1016/j.molcel.2005.10.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16337602">Kawamoto et al. (2005)</a> found that Polh was involved in Ig gene conversion in chicken B-lymphocyte precursors and in a chicken B-cell line. Polh -/- B cell lines exhibited hypersensitivity to ultraviolet irradiation, a significant decrease in the frequency of Ig gene conversion, and reduced double-strand break-induced homologous recombination compared with wildtype cells. Complementation with human POLH reversed these defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16337602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>DNA polymerase eta in eukaryotes is able to replicate through UV-induced cyclobutane pyrimidine dimers (CPDs), as shown by <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> and Johnson et al. (<a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">1999</a>, <a href="#9" class="mim-tip-reference" title="Johnson, R. E., Prakash, S., Prakash, L. <strong>Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Pol-eta.</strong> Science 283: 1001-1004, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9974380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9974380</a>] [<a href="https://doi.org/10.1126/science.283.5404.1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9974380">1999</a>). Pol-eta can also replicate through cisplatin-induced 1,2-d(GpG) cisplatin adducts (Pt-GGs) (<a href="#1" class="mim-tip-reference" title="Albertella, M. R., Green, C. M., Lehmann, A. R., O'Connor, M. J. <strong>A role for polymerase eta in the cellular tolerance to cisplatin-induced damage.</strong> Cancer Res. 65: 9799-9806, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16267001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16267001</a>] [<a href="https://doi.org/10.1158/0008-5472.CAN-05-1095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16267001">Albertella et al., 2005</a>) formed in a typical anticancer therapy with cisplatin (<a href="#18" class="mim-tip-reference" title="Wang, D., Lippard, S. J. <strong>Cellular processing of platinum anticancer drugs.</strong> Nature Rev. Drug Discov. 4: 307-320, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15789122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15789122</a>] [<a href="https://doi.org/10.1038/nrd1691" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15789122">Wang and Lippard, 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10398605+10385124+16267001+9974380+15789122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>DNA polymerase eta performs translesion synthesis past UV photoproducts and is deficient in cancer-prone xeroderma pigmentosum variant (XPV; <a href="/entry/278750">278750</a>) syndrome. The slight sensitivity of XPV cells to UV is dramatically enhanced by low concentrations of caffeine. Using DNA combing, <a href="#5" class="mim-tip-reference" title="Despras, E., Daboussi, F., Hyrien, O., Marheineke, K., Kannouche, P. L. <strong>ATR/Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells.</strong> Hum. Molec. Genet. 19: 1690-1701, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20123862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20123862</a>] [<a href="https://doi.org/10.1093/hmg/ddq046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20123862">Despras et al. (2010)</a> showed that translesion synthesis defect led to a strong reduction in the number of active replication forks and a high proportion of stalled forks in human cells. Extensive regions of single-strand DNA were formed during replication in irradiated XPV cells, leading to an overactivation of ATR/CHK1 (<a href="/entry/601215">601215</a>/<a href="/entry/603078">603078</a>) pathway after low UVC doses. Addition of a low concentration of caffeine post-irradiation significantly decreased CHK1 activation and abrogated DNA synthesis in XPV cells. While inhibition of CHK1 activity by 7-hydroxystaurosporine (UCN-01) prevented UVC-induced S-phase delay in wildtype cells, it aggravated replication defect in XPV cells by increasing fork stalling. Consequently, UCN-01 sensitized XPV cells to UVC as caffeine did. The authors concluded that POLH acts at stalled forks to resume their progression, preventing the requirement for efficient replication checkpoint after low UVC doses. In the absence of POLH, CHK1 kinase becomes essential for replication resumption by alternative pathways, via fork stabilization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20123862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#20" class="mim-tip-reference" title="Yuasa, M., Masutani, C., Eki, T., Hanaoka, F. <strong>Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene.</strong> Oncogene 19: 4721-4728, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11032022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11032022</a>] [<a href="https://doi.org/10.1038/sj.onc.1203842" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11032022">Yuasa et al. (2000)</a> demonstrated that the POLH gene contains 11 exons. All but 1 of the splice donor and acceptor sites contain consensus GT/AG dinucleotides; only the splice donor site in exon 11, which had the sequence CT, varied from the consensus pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11032022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#2" class="mim-tip-reference" title="Alt, A., Lammens, K., Chiocchini, C., Lammens, A., Pieck, J. C., Kuch, D., Hopfner, K.-P., Carell, T. <strong>Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta.</strong> Science 318: 967-970, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17991862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17991862</a>] [<a href="https://doi.org/10.1126/science.1148242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17991862">Alt et al. (2007)</a> presented a structural and biochemical analysis of how Pol-eta copies Pt-GG-containing DNA. The damaged DNA is bound in an open DNA binding rim. Nucleotidyl transfer requires the DNA to rotate into an active conformation, driven by hydrogen bonding of the templating base to the dNTP. For the 3-prime dG of the Pt-GG, this step is accomplished by a Watson-Crick basepair to dCTP and is biochemically efficient and accurate. In contrast, bypass of the 5-prime dG of the Pt-GG is less efficient and promiscuous for dCTP and dATP as a result of the presence of the rigid Pt crosslink. <a href="#2" class="mim-tip-reference" title="Alt, A., Lammens, K., Chiocchini, C., Lammens, A., Pieck, J. C., Kuch, D., Hopfner, K.-P., Carell, T. <strong>Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta.</strong> Science 318: 967-970, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17991862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17991862</a>] [<a href="https://doi.org/10.1126/science.1148242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17991862">Alt et al. (2007)</a> concluded that their analysis revealed the structural features that enable Pol-eta to replicate across strongly distorting DNA lesions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17991862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Silverstein, T. D., Johnson, R. E., Jain, R., Prakash, L., Prakash, S., Aggarwal, A. K. <strong>Structural basis for the suppression of skin cancers by DNA polymerase eta.</strong> Nature 465: 1039-1043, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20577207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20577207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20577207[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20577207">Silverstein et al. (2010)</a> presented the crystal structures of S. cerevisiae POLH, also known as RAD30, in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures revealed that the ability of PolH to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the 2 Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. <a href="#17" class="mim-tip-reference" title="Silverstein, T. D., Johnson, R. E., Jain, R., Prakash, L., Prakash, S., Aggarwal, A. K. <strong>Structural basis for the suppression of skin cancers by DNA polymerase eta.</strong> Nature 465: 1039-1043, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20577207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20577207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20577207[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20577207">Silverstein et al. (2010)</a> also showed by structural, biochemical, and genetic analyses that the 2 Ts are maintained in a stable configuration in the active site via interactions with gln55, arg73, and met74. <a href="#17" class="mim-tip-reference" title="Silverstein, T. D., Johnson, R. E., Jain, R., Prakash, L., Prakash, S., Aggarwal, A. K. <strong>Structural basis for the suppression of skin cancers by DNA polymerase eta.</strong> Nature 465: 1039-1043, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20577207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20577207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20577207[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20577207">Silverstein et al. (2010)</a> concluded that together, these features define the basis of PolH's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20577207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Biertumpfel, C., Zhao, Y., Kondo, Y., Ramon-Maiques, S., Gregory, M., Lee, J. Y., Masutani, C., Lehmann, A. R., Hanaoka, F., Yang, W. <strong>Structure and mechanism of human DNA polymerase eta.</strong> Nature 465: 1044-1048, 2010. Note: Erratum: Nature 476: 360 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20577208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20577208</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20577208[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20577208">Biertumpfel et al. (2010)</a> reported high-resolution crystal structures of human PolH at 4 consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. PolH acts like a molecular splint to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for 2-metal ion catalysis. Two residues conserved among PolH orthologs form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, 8 PolH missense mutations causing xeroderma pigmentosum type V (<a href="/entry/278750">278750</a>) can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provided an insight into the role of PolH in replicating through D loop and DNA fragile sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20577208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Nakamura, T., Zhao, Y., Yamagata, Y., Hua, Y., Yang, W. <strong>Watching DNA polymerase eta make a phosphodiester bond.</strong> Nature 487: 196-201, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22785315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22785315</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22785315[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11181" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22785315">Nakamura et al. (2012)</a> cocrystallized native human DNA polymerase eta, DNA, and dATP at pH 6.0 without Mg(2+). The polymerization reaction was initiated by exposing crystals to 1 mM Mg(2+) at pH 7.0, and stopped by freezing at desired time points for structural analysis. The substrates and 2 Mg(2+) ions were aligned within 40 seconds, but the bond formation was not evident until 80 seconds. From 80 to 300 seconds structures showed a mixture of decreasing substrate and increasing product of the nucleotidyl-transfer reaction. Transient electron densities indicated that deprotonation and an accompanying C2-prime-endo to C3-prime-endo conversion of the nucleophile 3-prime-OH are rate-limiting. A third Mg(2+) ion, which arrives with the new bond and stabilizes the intermediate state, may be an unappreciated feature of the 2-metal-ion mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22785315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By study of a human/rodent somatic cell hybrid mapping panel followed by fluorescence in situ hybridization, <a href="#20" class="mim-tip-reference" title="Yuasa, M., Masutani, C., Eki, T., Hanaoka, F. <strong>Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene.</strong> Oncogene 19: 4721-4728, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11032022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11032022</a>] [<a href="https://doi.org/10.1038/sj.onc.1203842" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11032022">Yuasa et al. (2000)</a> mapped the POLH gene to chromosome 6p21.1-p12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11032022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using sequencing of cDNA from XPV cell lines, <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> identified mutations in the POLH gene in all cell lines examined; see <a href="#0001">603968.0001</a> through <a href="#0005">603968.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10385124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 cell lines from XPV patients, <a href="#20" class="mim-tip-reference" title="Yuasa, M., Masutani, C., Eki, T., Hanaoka, F. <strong>Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene.</strong> Oncogene 19: 4721-4728, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11032022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11032022</a>] [<a href="https://doi.org/10.1038/sj.onc.1203842" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11032022">Yuasa et al. (2000)</a> identified mutations in the POLH gene; 3 were homozygous and 1 was a compound heterozygote. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11032022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> identified 8 mutations in cell lines of XPV patients, 7 of which would result in severely truncated POLH protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Limoli, C. L., Giedzinski, E., Morgan, W. F., Cleaver, J. E. <strong>Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.</strong> Proc. Nat. Acad. Sci. 97: 7939-7946, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10859352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10859352</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10859352[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.130182897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10859352">Limoli et al. (2000)</a> reported experimental results suggesting that the symptoms of elevated solar carcinogenesis in XPV patients may be associated with increased genomic rearrangements that result from double-strand breakage and rejoining in cells of the skin in which p53 (TP53; <a href="/entry/191170">191170</a>) is inactivated by UV-induced mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10859352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Broughton, B. C., Cordonnier, A., Kleijer, W. J., Jaspers, N. G. J., Fawcett, H., Raams, A., Garritsen, V. H., Stary, A., Avril, M.-F., Boudsocq, F., Masutani, C., Hanaoka, F., Fuchs, R. P., Sarasin, A., Lehmann, A. R. <strong>Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients.</strong> Proc. Nat. Acad. Sci. 99: 815-820, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11773631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11773631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11773631[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.022473899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11773631">Broughton et al. (2002)</a> analyzed mutations in the POLH gene in 21 patients with XPV who varied in age from 7 to 69 years. They identified 16 mutations that fell into 3 categories. Many of the mutations resulted in severe truncations of the protein and were effectively null alleles. However, 5 missense mutations were located in the conserved catalytic domain of the protein. Extracts of cells falling into these 2 categories were defective in the ability to carry out translesion synthesis (TLS) past sites of DNA damage. Three mutations caused truncations of the C terminus such that the catalytic domains were intact, and extracts from these cells were able to carry out TLS. Based on their previous work, however, <a href="#4" class="mim-tip-reference" title="Broughton, B. C., Cordonnier, A., Kleijer, W. J., Jaspers, N. G. J., Fawcett, H., Raams, A., Garritsen, V. H., Stary, A., Avril, M.-F., Boudsocq, F., Masutani, C., Hanaoka, F., Fuchs, R. P., Sarasin, A., Lehmann, A. R. <strong>Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients.</strong> Proc. Nat. Acad. Sci. 99: 815-820, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11773631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11773631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11773631[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.022473899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11773631">Broughton et al. (2002)</a> anticipated that protein in these cells would not be localized in the nucleus or would not be relocalized into replication foci during DNA replication. The spectrum of both missense and truncating mutations was markedly skewed toward the N-terminal half of the protein. Two of the missense mutations were predicted to affect the interaction with DNA, while the others were likely to disrupt the 3-dimensional structure of the protein. There was a wide variability in clinical features among patients, which was not obviously related to the site or type of mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11773631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0001 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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POLH, 13-BP DEL, NT343
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2127773185 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2127773185;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2127773185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2127773185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006242 OR RCV005089189" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006242, RCV005089189" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006242...</a>
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<span class="mim-text-font">
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP30RO, <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> identified deletion of 13 nucleotides between positions 343 and 355. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10385124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> reported the same 13-bp deletion as occurring at nucleotides 104-116 in cell line XP30R0 from a patient of Lebanese origin. They noted that the mutation would result in the truncation of the POLH protein at position 35. Only the mutant allele was observed in this cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0002" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0002 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</h4>
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<span class="mim-text-font">
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POLH, 4-BP DEL, NT289
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2127773120 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2127773120;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2127773120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2127773120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006243" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006243" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006243</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP4BE, <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> identified deletion of 4 nucleotides between positions 289 and 292. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10385124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<a id="0003" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0003 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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POLH, 2-BP DEL, NT770
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006244" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006244" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006244</a>
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</span>
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<span class="mim-text-font">
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP7TA, <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> identified deletion of 2 nucleotides at position 770-771. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10385124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0004 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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POLH, GLU306TER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908562 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908562;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006245" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006245" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006245</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP2SA, <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> identified a G-to-T mutation at nucleotide 1153 which resulted in a glu306-to-ter mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10385124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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POLH, DEL AND TRP297TER
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006246" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006246" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006246</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP1RO, <a href="#13" class="mim-tip-reference" title="Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F. <strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong> Nature 399: 700-704, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>] [<a href="https://doi.org/10.1038/21447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10385124">Masutani et al. (1999)</a> identified a large genomic deletion that was not fully characterized. On the other allele, there was G-to-A mutation at nucleotide 1127 which resulted in a trp297-to-ter mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10385124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</div>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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POLH, VAL125TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908563 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908563;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121908563?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006247 OR RCV003555934" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006247, RCV003555934" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006247...</a>
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<span class="mim-text-font">
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell lines XP1CH and XP2CH, derived from 2 sibs of Russian-Armenian origin with XPV who were the offspring of a first-cousin marriage, <a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> identified a C-to-T transition at nucleotide 376 of the POLH gene, resulting in the substitution of a premature termination codon for valine at codon 125. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908564 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908564;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121908564?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006248 OR RCV003555935" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006248, RCV003555935" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006248...</a>
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP115LO, derived from an individual of Iranian origin who was the offspring of a first-cousin marriage, <a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> identified a C-to-T transition at nucleotide 1117, which created a premature termination codon in place of valine at codon 372. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2127799895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2127799895;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2127799895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2127799895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006249" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006249" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006249</a>
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP5MA, derived from a patient of German ancestry, <a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> identified a 104-bp deletion at nucleotides 661-764 of the POLH gene, resulting in a frameshift at lys220. Only the mutant allele was observed in this cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0010" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0010 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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POLH, 1-BP DEL, 207G
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1176350430 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1176350430;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1176350430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1176350430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006250 OR RCV005089190" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006250, RCV005089190" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006250...</a>
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP6DU, derived from a patient of Scottish ancestry, <a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> identified a mutation on each allele. One was a -1 deletion of a G at nucleotide 207, resulting in a frameshift at lys69; the other was a 3-bp deletion at nucleotides 222-224 (<a href="#0011">603968.0011</a>), resulting in an in-frame deletion of leu at codon 75. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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POLH, 3-BP DEL, NT222
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1426687865 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1426687865;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1426687865?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1426687865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1426687865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006251" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006251" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006251</a>
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<span class="mim-text-font">
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<p>In the XPV (<a href="/entry/278750">278750</a>) cell line XP6DU, <a href="#8" class="mim-tip-reference" title="Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L. <strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong> Science 285: 263-265, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>] [<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398605">Johnson et al. (1999)</a> identified a mutation on each allele. One mutation was a 3-bp deletion at nucleotides 222-224, resulting in an in-frame deletion of leu at codon 75; the other mutation was a frameshift at lys69 (<a href="#0010">603968.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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POLH, LYS535GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs56307355 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs56307355;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs56307355?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs56307355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs56307355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006252 OR RCV000899778 OR RCV002257357 OR RCV002298435 OR RCV003944804" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006252, RCV000899778, RCV002257357, RCV002298435, RCV003944804" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006252...</a>
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<p>In a Japanese patient with XPV (<a href="/entry/278750">278750</a>) and 1 of his parents, <a href="#7" class="mim-tip-reference" title="Itoh, T., Linn, S., Kamide, R., Tokushige, H., Katori, N., Hosaka, Y., Yamaizumi, M. <strong>Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation.</strong> J. Invest. Derm. 115: 981-985, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11121129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11121129</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2000.00154.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11121129">Itoh et al. (2000)</a> identified an A-G transition at nucleotide 1840 of the POLH cDNA, which resulted in a lys535-to-glu (K535E) missense mutation. This basic lysine residue is conserved between human and mouse (<a href="#19" class="mim-tip-reference" title="Yamada, A., Masutani, C., Iwai, S., Hanaoka, F. <strong>Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta.</strong> Nucleic Acids Res. 28: 2473-2480, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10871396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10871396</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10871396[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/nar/28.13.2473" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10871396">Yamada et al., 2000</a>). The lys535-to-glu mutation likely affects the conformation and functionality of the DNA polymerase. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10871396+11121129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0013" class="mim-anchor"></a>
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<strong>.0013 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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POLH, LYS589THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908565 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908565;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121908565?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908565" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908565" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006253" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006253" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006253</a>
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<p>In a Japanese patient with XPV (<a href="/entry/278750">278750</a>) and 1 parent, <a href="#7" class="mim-tip-reference" title="Itoh, T., Linn, S., Kamide, R., Tokushige, H., Katori, N., Hosaka, Y., Yamaizumi, M. <strong>Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation.</strong> J. Invest. Derm. 115: 981-985, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11121129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11121129</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2000.00154.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11121129">Itoh et al. (2000)</a> identified an A-C transversion at nucleotide 2003 of the POLH cDNA, which resulted in a lys589-to-thr (K589T) missense mutation. This basic lysine residue is conserved between human and mouse (<a href="#19" class="mim-tip-reference" title="Yamada, A., Masutani, C., Iwai, S., Hanaoka, F. <strong>Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta.</strong> Nucleic Acids Res. 28: 2473-2480, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10871396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10871396</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10871396[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/nar/28.13.2473" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10871396">Yamada et al., 2000</a>). The lys589-to-thr mutation likely affects the conformation and functionality of the DNA polymerase. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10871396+11121129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1158/0008-5472.CAN-05-1095" target="_blank">Full Text</a>]
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<a id="Alt2007" class="mim-anchor"></a>
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Alt, A., Lammens, K., Chiocchini, C., Lammens, A., Pieck, J. C., Kuch, D., Hopfner, K.-P., Carell, T.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17991862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17991862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17991862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1148242" target="_blank">Full Text</a>]
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<a id="Biertumpfel2010" class="mim-anchor"></a>
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Biertumpfel, C., Zhao, Y., Kondo, Y., Ramon-Maiques, S., Gregory, M., Lee, J. Y., Masutani, C., Lehmann, A. R., Hanaoka, F., Yang, W.
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<strong>Structure and mechanism of human DNA polymerase eta.</strong>
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Nature 465: 1044-1048, 2010. Note: Erratum: Nature 476: 360 only, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20577208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20577208</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20577208[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20577208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature09196" target="_blank">Full Text</a>]
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<a id="Broughton2002" class="mim-anchor"></a>
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Broughton, B. C., Cordonnier, A., Kleijer, W. J., Jaspers, N. G. J., Fawcett, H., Raams, A., Garritsen, V. H., Stary, A., Avril, M.-F., Boudsocq, F., Masutani, C., Hanaoka, F., Fuchs, R. P., Sarasin, A., Lehmann, A. R.
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<strong>Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11773631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11773631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11773631[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11773631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.022473899" target="_blank">Full Text</a>]
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<a id="Despras2010" class="mim-anchor"></a>
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Despras, E., Daboussi, F., Hyrien, O., Marheineke, K., Kannouche, P. L.
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<strong>ATR/Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells.</strong>
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Hum. Molec. Genet. 19: 1690-1701, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20123862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20123862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20123862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq046" target="_blank">Full Text</a>]
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Haracska, L., Yu, S.-L., Johnson, R. E., Prakash, L., Prakash, S.
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<strong>Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta.</strong>
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Nature Genet. 25: 458-461, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10932195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10932195</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10932195" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/78169" target="_blank">Full Text</a>]
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<a id="Itoh2000" class="mim-anchor"></a>
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Itoh, T., Linn, S., Kamide, R., Tokushige, H., Katori, N., Hosaka, Y., Yamaizumi, M.
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<strong>Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation.</strong>
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J. Invest. Derm. 115: 981-985, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11121129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11121129</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11121129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1046/j.1523-1747.2000.00154.x" target="_blank">Full Text</a>]
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<a id="Johnson1999" class="mim-anchor"></a>
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Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L.
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<strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong>
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Science 285: 263-265, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398605</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10398605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.285.5425.263" target="_blank">Full Text</a>]
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Johnson, R. E., Prakash, S., Prakash, L.
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<strong>Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Pol-eta.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9974380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9974380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9974380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.283.5404.1001" target="_blank">Full Text</a>]
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<a id="Kawamoto2005" class="mim-anchor"></a>
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Kawamoto, T., Araki, K., Sonoda, E., Yamashita, Y. M., Harada, K., Kikuchi, K., Masutani, C., Hanaoka, F., Nozaki, K., Hashimoto, N., Takeda, S.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16337602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16337602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16337602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.molcel.2005.10.016" target="_blank">Full Text</a>]
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Limoli, C. L., Giedzinski, E., Morgan, W. F., Cleaver, J. E.
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<strong>Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.</strong>
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[<a href="https://doi.org/10.1073/pnas.130182897" target="_blank">Full Text</a>]
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Masutani, C., Araki, M., Yamada, A., Kusumoto, R., Nogimori, T., Maekawa, T., Iwai, S., Hanaoka, F.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/emboj/18.12.3491" target="_blank">Full Text</a>]
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Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F.
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<strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong>
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Nature 399: 700-704, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10385124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10385124</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10385124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/21447" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Matsuda2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F., Kunkel, T. A.
|
|
<strong>Low fidelity DNA synthesis by human DNA polymerase-eta.</strong>
|
|
Nature 404: 1011-1013, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10801132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10801132</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10801132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/35010014" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="McIlwraith2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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McIlwraith, M. J., Vaisman, A., Liu, Y., Fanning, E., Woodgate, R., West, S. C.
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|
<strong>Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination.</strong>
|
|
Molec. Cell 20: 783-792, 2005. Note: Erratum: Molec. Cell 21: 445 only, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16337601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16337601</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16337601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.molcel.2005.10.001" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Nakamura2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nakamura, T., Zhao, Y., Yamagata, Y., Hua, Y., Yang, W.
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<strong>Watching DNA polymerase eta make a phosphodiester bond.</strong>
|
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Nature 487: 196-201, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22785315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22785315</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22785315[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22785315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature11181" target="_blank">Full Text</a>]
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Silverstein2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Silverstein, T. D., Johnson, R. E., Jain, R., Prakash, L., Prakash, S., Aggarwal, A. K.
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<strong>Structural basis for the suppression of skin cancers by DNA polymerase eta.</strong>
|
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Nature 465: 1039-1043, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20577207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20577207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20577207[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20577207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature09104" target="_blank">Full Text</a>]
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Wang2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, D., Lippard, S. J.
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<strong>Cellular processing of platinum anticancer drugs.</strong>
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Nature Rev. Drug Discov. 4: 307-320, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15789122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15789122</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15789122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nrd1691" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Yamada2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yamada, A., Masutani, C., Iwai, S., Hanaoka, F.
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<strong>Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta.</strong>
|
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Nucleic Acids Res. 28: 2473-2480, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10871396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10871396</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10871396[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10871396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/nar/28.13.2473" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Yuasa2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yuasa, M., Masutani, C., Eki, T., Hanaoka, F.
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<strong>Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene.</strong>
|
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Oncogene 19: 4721-4728, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11032022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11032022</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11032022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.onc.1203842" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 09/04/2012
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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George E. Tiller - updated : 12/1/2011<br>Ada Hamosh - updated : 8/17/2010<br>Patricia A. Hartz - updated : 1/24/2006<br>Victor A. McKusick - updated : 2/6/2002<br>Gary A. Bellus - updated : 4/11/2001<br>Victor A. McKusick - updated : 1/9/2001<br>Victor A. McKusick - updated : 9/6/2000<br>Ada Hamosh - updated : 8/1/2000<br>Ada Hamosh - updated : 6/9/2000<br>Ada Hamosh - updated : 7/9/1999
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 7/8/1999
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/28/2016
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 09/04/2012<br>alopez : 12/5/2011<br>alopez : 12/5/2011<br>terry : 12/1/2011<br>alopez : 9/7/2011<br>alopez : 8/20/2010<br>terry : 8/17/2010<br>carol : 6/3/2009<br>terry : 5/20/2008<br>alopez : 11/28/2007<br>alopez : 11/28/2007<br>mgross : 2/21/2006<br>mgross : 2/2/2006<br>terry : 1/24/2006<br>carol : 8/13/2004<br>cwells : 11/7/2003<br>mgross : 2/11/2002<br>terry : 2/6/2002<br>cwells : 4/12/2001<br>cwells : 4/11/2001<br>mcapotos : 1/22/2001<br>mcapotos : 1/16/2001<br>terry : 1/9/2001<br>mcapotos : 9/6/2000<br>alopez : 9/1/2000<br>alopez : 8/2/2000<br>terry : 8/1/2000<br>alopez : 6/16/2000<br>terry : 6/9/2000<br>carol : 2/23/2000<br>carol : 2/23/2000<br>alopez : 11/23/1999<br>alopez : 10/13/1999<br>carol : 7/12/1999<br>terry : 7/9/1999<br>carol : 7/8/1999<br>carol : 7/8/1999
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 603968
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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POLYMERASE, DNA, ETA; POLH
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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RAD30, S. CEREVISIAE, HOMOLOG OF, A; RAD30A
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: POLH</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 6p21.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:43,576,185-43,620,523 </span>
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</em>
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</strong>
|
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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6p21.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Xeroderma pigmentosum, variant type
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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278750
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using an improved cell-free assay for translesion DNA synthesis, Masutani et al. (1999) isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in xeroderma pigmentosum variant (XPV; 278750) cell extracts. Masutani et al. (1999) demonstrated that this polymerase, symbolized POLH, is a human homolog of the yeast Rad30 protein identified as DNA polymerase eta (Johnson et al., 1999). POLH and yeast Rad30 are members of a family of damage-bypass replication proteins which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. The XPV cDNA encodes a protein of 713 amino acids with a calculated molecular mass of 78.4 kD. The amino acid sequences of the human POLH and yeast Rad30 proteins are 19% identical and 31.9% similar. Masutani et al. (1999) found that POLH shares 7 conserved domains with other proteins of S. pombe, Arabidopsis thaliana, C. elegans, and S. cerevisiae. No known DNA polymerase motifs were identified in DNA polymerase eta. Northern blot analysis of RNAs from 5 XPV cell lines revealed 2 with major decreases in band intensity. Recombinant human DNA polymerase eta corrected the inability of XPV cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. </p><p>Johnson et al. (1999) independently cloned the human DNA polymerase eta gene, which they called hRAD30, by homology cloning of S. cerevisiae RAD30. DNA polymerase eta is involved in the error-free bypass of ultraviolet light damage. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Oxidative damage to DNA had been proposed to have a role in cancer and aging. Oxygen-free radicals formed during normal aerobic cellular metabolism attack bases in DNA, and a 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the adducts formed. Eukaryotic replicative DNA polymerases replicate DNA containing 8-oxoG by inserting an adenine opposite the lesion; consequently, 8-oxoG is highly mutagenic and causes G:C to T:A transversions. Genetic studies in yeast have indicated a role for mismatch repair in minimizing the incidence of these mutations. The gene RAD30 of S. cerevisiae encodes a DNA polymerase, Pol-eta, that efficiently replicates DNA containing a cis-syn thymine-thymine dimer by inserting 2 adenines across from the dimer. Haracska et al. (2000) showed that yeast and human POL-eta replicate DNA containing 8-oxoG efficiently and accurately by inserting a cytosine across from the lesion and by proficiently extending from this basepair. Consistent with these biochemical studies, a synergistic increase in the rate of spontaneous mutations occurs in the absence of POL-eta in the yeast ogg1 (601982) deletion mutant. Haracska et al. (2000) stated that their results suggested an additional role for POL-eta in the prevention of internal cancers in humans that would otherwise result from the mutagenic replication of 8-oxoG in DNA. </p><p>Matsuda et al. (2000) demonstrated that human POLH copies undamaged DNA with much lower fidelity than any other template-dependent DNA polymerase studied. POLH lacks an intrinsic proofreading exonuclease activity and, depending on the mismatch, makes 1 base substitution error for every 18 to 380 nucleotides synthesized. This very low fidelity indicates a relaxed requirement for correct basepairing geometry and indicates that the function of POLH may be tightly controlled to prevent potentially mutagenic DNA synthesis. </p><p>To overcome the catastrophic consequences associated with the demise of stalled replication forks, translesional synthesis polymerases promote DNA synthesis past lesions. Alternatively, a stalled fork may collapse and undergo repair by homologous recombination. McIlwraith et al. (2005) found that human POLH extended DNA synthesis past lesions following formation of a D-loop structure, with the invading strand serving as primer. POLH showed highest specificity for the D loop and weaker association with replication forks and single- and double-stranded DNA. POLH interacted with the recombinase RAD51 (179617) in HeLa cells following DNA damage, and RAD51 stimulated the DNA extension activity of POLH. Extracts from an XPV cell line exhibited severely reduced D-loop extension activity. McIlwraith et al. (2005) concluded that POLH promotes translesional synthesis at stalled replication forks and reinitiates DNA synthesis by homologous recombination repair. </p><p>B lymphocytes diversify their immunoglobulin-variable (IgV) genes through homologous recombination-mediated Ig gene conversion. Kawamoto et al. (2005) found that Polh was involved in Ig gene conversion in chicken B-lymphocyte precursors and in a chicken B-cell line. Polh -/- B cell lines exhibited hypersensitivity to ultraviolet irradiation, a significant decrease in the frequency of Ig gene conversion, and reduced double-strand break-induced homologous recombination compared with wildtype cells. Complementation with human POLH reversed these defects. </p><p>DNA polymerase eta in eukaryotes is able to replicate through UV-induced cyclobutane pyrimidine dimers (CPDs), as shown by Masutani et al. (1999) and Johnson et al. (1999, 1999). Pol-eta can also replicate through cisplatin-induced 1,2-d(GpG) cisplatin adducts (Pt-GGs) (Albertella et al., 2005) formed in a typical anticancer therapy with cisplatin (Wang and Lippard, 2005). </p><p>DNA polymerase eta performs translesion synthesis past UV photoproducts and is deficient in cancer-prone xeroderma pigmentosum variant (XPV; 278750) syndrome. The slight sensitivity of XPV cells to UV is dramatically enhanced by low concentrations of caffeine. Using DNA combing, Despras et al. (2010) showed that translesion synthesis defect led to a strong reduction in the number of active replication forks and a high proportion of stalled forks in human cells. Extensive regions of single-strand DNA were formed during replication in irradiated XPV cells, leading to an overactivation of ATR/CHK1 (601215/603078) pathway after low UVC doses. Addition of a low concentration of caffeine post-irradiation significantly decreased CHK1 activation and abrogated DNA synthesis in XPV cells. While inhibition of CHK1 activity by 7-hydroxystaurosporine (UCN-01) prevented UVC-induced S-phase delay in wildtype cells, it aggravated replication defect in XPV cells by increasing fork stalling. Consequently, UCN-01 sensitized XPV cells to UVC as caffeine did. The authors concluded that POLH acts at stalled forks to resume their progression, preventing the requirement for efficient replication checkpoint after low UVC doses. In the absence of POLH, CHK1 kinase becomes essential for replication resumption by alternative pathways, via fork stabilization. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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|
<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Yuasa et al. (2000) demonstrated that the POLH gene contains 11 exons. All but 1 of the splice donor and acceptor sites contain consensus GT/AG dinucleotides; only the splice donor site in exon 11, which had the sequence CT, varied from the consensus pattern. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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|
Alt et al. (2007) presented a structural and biochemical analysis of how Pol-eta copies Pt-GG-containing DNA. The damaged DNA is bound in an open DNA binding rim. Nucleotidyl transfer requires the DNA to rotate into an active conformation, driven by hydrogen bonding of the templating base to the dNTP. For the 3-prime dG of the Pt-GG, this step is accomplished by a Watson-Crick basepair to dCTP and is biochemically efficient and accurate. In contrast, bypass of the 5-prime dG of the Pt-GG is less efficient and promiscuous for dCTP and dATP as a result of the presence of the rigid Pt crosslink. Alt et al. (2007) concluded that their analysis revealed the structural features that enable Pol-eta to replicate across strongly distorting DNA lesions. </p><p>Silverstein et al. (2010) presented the crystal structures of S. cerevisiae POLH, also known as RAD30, in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures revealed that the ability of PolH to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the 2 Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. Silverstein et al. (2010) also showed by structural, biochemical, and genetic analyses that the 2 Ts are maintained in a stable configuration in the active site via interactions with gln55, arg73, and met74. Silverstein et al. (2010) concluded that together, these features define the basis of PolH's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans. </p><p>Biertumpfel et al. (2010) reported high-resolution crystal structures of human PolH at 4 consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. PolH acts like a molecular splint to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for 2-metal ion catalysis. Two residues conserved among PolH orthologs form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, 8 PolH missense mutations causing xeroderma pigmentosum type V (278750) can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provided an insight into the role of PolH in replicating through D loop and DNA fragile sites. </p><p>Nakamura et al. (2012) cocrystallized native human DNA polymerase eta, DNA, and dATP at pH 6.0 without Mg(2+). The polymerization reaction was initiated by exposing crystals to 1 mM Mg(2+) at pH 7.0, and stopped by freezing at desired time points for structural analysis. The substrates and 2 Mg(2+) ions were aligned within 40 seconds, but the bond formation was not evident until 80 seconds. From 80 to 300 seconds structures showed a mixture of decreasing substrate and increasing product of the nucleotidyl-transfer reaction. Transient electron densities indicated that deprotonation and an accompanying C2-prime-endo to C3-prime-endo conversion of the nucleophile 3-prime-OH are rate-limiting. A third Mg(2+) ion, which arrives with the new bond and stabilizes the intermediate state, may be an unappreciated feature of the 2-metal-ion mechanism. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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|
<p>By study of a human/rodent somatic cell hybrid mapping panel followed by fluorescence in situ hybridization, Yuasa et al. (2000) mapped the POLH gene to chromosome 6p21.1-p12. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Using sequencing of cDNA from XPV cell lines, Masutani et al. (1999) identified mutations in the POLH gene in all cell lines examined; see 603968.0001 through 603968.0005. </p><p>In 4 cell lines from XPV patients, Yuasa et al. (2000) identified mutations in the POLH gene; 3 were homozygous and 1 was a compound heterozygote. </p><p>Johnson et al. (1999) identified 8 mutations in cell lines of XPV patients, 7 of which would result in severely truncated POLH protein. </p><p>Limoli et al. (2000) reported experimental results suggesting that the symptoms of elevated solar carcinogenesis in XPV patients may be associated with increased genomic rearrangements that result from double-strand breakage and rejoining in cells of the skin in which p53 (TP53; 191170) is inactivated by UV-induced mutations. </p><p>Broughton et al. (2002) analyzed mutations in the POLH gene in 21 patients with XPV who varied in age from 7 to 69 years. They identified 16 mutations that fell into 3 categories. Many of the mutations resulted in severe truncations of the protein and were effectively null alleles. However, 5 missense mutations were located in the conserved catalytic domain of the protein. Extracts of cells falling into these 2 categories were defective in the ability to carry out translesion synthesis (TLS) past sites of DNA damage. Three mutations caused truncations of the C terminus such that the catalytic domains were intact, and extracts from these cells were able to carry out TLS. Based on their previous work, however, Broughton et al. (2002) anticipated that protein in these cells would not be localized in the nucleus or would not be relocalized into replication foci during DNA replication. The spectrum of both missense and truncating mutations was markedly skewed toward the N-terminal half of the protein. Two of the missense mutations were predicted to affect the interaction with DNA, while the others were likely to disrupt the 3-dimensional structure of the protein. There was a wide variability in clinical features among patients, which was not obviously related to the site or type of mutation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>13 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0001 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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POLH, 13-BP DEL, NT343
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<br />
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SNP: rs2127773185,
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|
ClinVar: RCV000006242, RCV005089189
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell line XP30RO, Masutani et al. (1999) identified deletion of 13 nucleotides between positions 343 and 355. </p><p>Johnson et al. (1999) reported the same 13-bp deletion as occurring at nucleotides 104-116 in cell line XP30R0 from a patient of Lebanese origin. They noted that the mutation would result in the truncation of the POLH protein at position 35. Only the mutant allele was observed in this cell line. </p>
|
|
</span>
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</div>
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<div>
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|
<br />
|
|
</div>
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</div>
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<div>
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|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLH, 4-BP DEL, NT289
|
|
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|
|
|
<br />
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|
|
|
SNP: rs2127773120,
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|
|
|
|
|
|
ClinVar: RCV000006243
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell line XP4BE, Masutani et al. (1999) identified deletion of 4 nucleotides between positions 289 and 292. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
POLH, 2-BP DEL, NT770
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|
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|
|
<br />
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|
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|
|
ClinVar: RCV000006244
|
|
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|
|
|
</span>
|
|
</div>
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell line XP7TA, Masutani et al. (1999) identified deletion of 2 nucleotides at position 770-771. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLH, GLU306TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908562,
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|
|
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|
|
ClinVar: RCV000006245
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell line XP2SA, Masutani et al. (1999) identified a G-to-T mutation at nucleotide 1153 which resulted in a glu306-to-ter mutation. </p>
|
|
</span>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLH, DEL AND TRP297TER
|
|
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|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000006246
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell line XP1RO, Masutani et al. (1999) identified a large genomic deletion that was not fully characterized. On the other allele, there was G-to-A mutation at nucleotide 1127 which resulted in a trp297-to-ter mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLH, VAL125TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908563,
|
|
|
|
|
|
gnomAD: rs121908563,
|
|
|
|
|
|
ClinVar: RCV000006247, RCV003555934
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell lines XP1CH and XP2CH, derived from 2 sibs of Russian-Armenian origin with XPV who were the offspring of a first-cousin marriage, Johnson et al. (1999) identified a C-to-T transition at nucleotide 376 of the POLH gene, resulting in the substitution of a premature termination codon for valine at codon 125. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLH, VAL372TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908564,
|
|
|
|
|
|
gnomAD: rs121908564,
|
|
|
|
|
|
ClinVar: RCV000006248, RCV003555935
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell line XP115LO, derived from an individual of Iranian origin who was the offspring of a first-cousin marriage, Johnson et al. (1999) identified a C-to-T transition at nucleotide 1117, which created a premature termination codon in place of valine at codon 372. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLH, 104-BP DEL, NT661
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2127799895,
|
|
|
|
|
|
|
|
ClinVar: RCV000006249
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the XPV (278750) cell line XP5MA, derived from a patient of German ancestry, Johnson et al. (1999) identified a 104-bp deletion at nucleotides 661-764 of the POLH gene, resulting in a frameshift at lys220. Only the mutant allele was observed in this cell line. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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POLH, 1-BP DEL, 207G
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<br />
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SNP: rs1176350430,
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ClinVar: RCV000006250, RCV005089190
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In the XPV (278750) cell line XP6DU, derived from a patient of Scottish ancestry, Johnson et al. (1999) identified a mutation on each allele. One was a -1 deletion of a G at nucleotide 207, resulting in a frameshift at lys69; the other was a 3-bp deletion at nucleotides 222-224 (603968.0011), resulting in an in-frame deletion of leu at codon 75. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0011 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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POLH, 3-BP DEL, NT222
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<br />
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SNP: rs1426687865,
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gnomAD: rs1426687865,
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ClinVar: RCV000006251
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In the XPV (278750) cell line XP6DU, Johnson et al. (1999) identified a mutation on each allele. One mutation was a 3-bp deletion at nucleotides 222-224, resulting in an in-frame deletion of leu at codon 75; the other mutation was a frameshift at lys69 (603968.0010). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0012 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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POLH, LYS535GLU
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<br />
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SNP: rs56307355,
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|
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gnomAD: rs56307355,
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|
|
ClinVar: RCV000006252, RCV000899778, RCV002257357, RCV002298435, RCV003944804
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a Japanese patient with XPV (278750) and 1 of his parents, Itoh et al. (2000) identified an A-G transition at nucleotide 1840 of the POLH cDNA, which resulted in a lys535-to-glu (K535E) missense mutation. This basic lysine residue is conserved between human and mouse (Yamada et al., 2000). The lys535-to-glu mutation likely affects the conformation and functionality of the DNA polymerase. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0013 XERODERMA PIGMENTOSUM, VARIANT TYPE</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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POLH, LYS589THR
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<br />
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SNP: rs121908565,
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gnomAD: rs121908565,
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ClinVar: RCV000006253
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</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Japanese patient with XPV (278750) and 1 parent, Itoh et al. (2000) identified an A-C transversion at nucleotide 2003 of the POLH cDNA, which resulted in a lys589-to-thr (K589T) missense mutation. This basic lysine residue is conserved between human and mouse (Yamada et al., 2000). The lys589-to-thr mutation likely affects the conformation and functionality of the DNA polymerase. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Albertella, M. R., Green, C. M., Lehmann, A. R., O'Connor, M. J.
|
|
<strong>A role for polymerase eta in the cellular tolerance to cisplatin-induced damage.</strong>
|
|
Cancer Res. 65: 9799-9806, 2005.
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[PubMed: 16267001]
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[Full Text: https://doi.org/10.1158/0008-5472.CAN-05-1095]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Alt, A., Lammens, K., Chiocchini, C., Lammens, A., Pieck, J. C., Kuch, D., Hopfner, K.-P., Carell, T.
|
|
<strong>Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta.</strong>
|
|
Science 318: 967-970, 2007.
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[PubMed: 17991862]
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[Full Text: https://doi.org/10.1126/science.1148242]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Biertumpfel, C., Zhao, Y., Kondo, Y., Ramon-Maiques, S., Gregory, M., Lee, J. Y., Masutani, C., Lehmann, A. R., Hanaoka, F., Yang, W.
|
|
<strong>Structure and mechanism of human DNA polymerase eta.</strong>
|
|
Nature 465: 1044-1048, 2010. Note: Erratum: Nature 476: 360 only, 2011.
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[PubMed: 20577208]
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[Full Text: https://doi.org/10.1038/nature09196]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Broughton, B. C., Cordonnier, A., Kleijer, W. J., Jaspers, N. G. J., Fawcett, H., Raams, A., Garritsen, V. H., Stary, A., Avril, M.-F., Boudsocq, F., Masutani, C., Hanaoka, F., Fuchs, R. P., Sarasin, A., Lehmann, A. R.
|
|
<strong>Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 815-820, 2002.
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[PubMed: 11773631]
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[Full Text: https://doi.org/10.1073/pnas.022473899]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Despras, E., Daboussi, F., Hyrien, O., Marheineke, K., Kannouche, P. L.
|
|
<strong>ATR/Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells.</strong>
|
|
Hum. Molec. Genet. 19: 1690-1701, 2010.
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|
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|
|
[PubMed: 20123862]
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[Full Text: https://doi.org/10.1093/hmg/ddq046]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Haracska, L., Yu, S.-L., Johnson, R. E., Prakash, L., Prakash, S.
|
|
<strong>Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta.</strong>
|
|
Nature Genet. 25: 458-461, 2000.
|
|
|
|
|
|
[PubMed: 10932195]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/78169]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Itoh, T., Linn, S., Kamide, R., Tokushige, H., Katori, N., Hosaka, Y., Yamaizumi, M.
|
|
<strong>Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation.</strong>
|
|
J. Invest. Derm. 115: 981-985, 2000.
|
|
|
|
|
|
[PubMed: 11121129]
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|
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|
|
[Full Text: https://doi.org/10.1046/j.1523-1747.2000.00154.x]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, R. E., Kondratick, C. M., Prakash, S., Prakash, L.
|
|
<strong>hRAD30 mutations in the variant form of xeroderma pigmentosum.</strong>
|
|
Science 285: 263-265, 1999.
|
|
|
|
|
|
[PubMed: 10398605]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.285.5425.263]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, R. E., Prakash, S., Prakash, L.
|
|
<strong>Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Pol-eta.</strong>
|
|
Science 283: 1001-1004, 1999.
|
|
|
|
|
|
[PubMed: 9974380]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.283.5404.1001]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kawamoto, T., Araki, K., Sonoda, E., Yamashita, Y. M., Harada, K., Kikuchi, K., Masutani, C., Hanaoka, F., Nozaki, K., Hashimoto, N., Takeda, S.
|
|
<strong>Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis.</strong>
|
|
Molec. Cell 20: 793-799, 2005.
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|
|
|
|
[PubMed: 16337602]
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|
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[Full Text: https://doi.org/10.1016/j.molcel.2005.10.016]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Limoli, C. L., Giedzinski, E., Morgan, W. F., Cleaver, J. E.
|
|
<strong>Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 7939-7946, 2000.
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|
|
|
|
|
[PubMed: 10859352]
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|
|
[Full Text: https://doi.org/10.1073/pnas.130182897]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Masutani, C., Araki, M., Yamada, A., Kusumoto, R., Nogimori, T., Maekawa, T., Iwai, S., Hanaoka, F.
|
|
<strong>Xeroderma pigmentosum variant (XP-V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity.</strong>
|
|
EMBO J. 18: 3491-3501, 1999.
|
|
|
|
|
|
[PubMed: 10369688]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/18.12.3491]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., Hanaoka, F.
|
|
<strong>The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.</strong>
|
|
Nature 399: 700-704, 1999.
|
|
|
|
|
|
[PubMed: 10385124]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/21447]
|
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|
|
</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F., Kunkel, T. A.
|
|
<strong>Low fidelity DNA synthesis by human DNA polymerase-eta.</strong>
|
|
Nature 404: 1011-1013, 2000.
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|
|
|
|
|
[PubMed: 10801132]
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|
|
|
|
|
[Full Text: https://doi.org/10.1038/35010014]
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|
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</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
McIlwraith, M. J., Vaisman, A., Liu, Y., Fanning, E., Woodgate, R., West, S. C.
|
|
<strong>Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination.</strong>
|
|
Molec. Cell 20: 783-792, 2005. Note: Erratum: Molec. Cell 21: 445 only, 2006.
|
|
|
|
|
|
[PubMed: 16337601]
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|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.molcel.2005.10.001]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakamura, T., Zhao, Y., Yamagata, Y., Hua, Y., Yang, W.
|
|
<strong>Watching DNA polymerase eta make a phosphodiester bond.</strong>
|
|
Nature 487: 196-201, 2012.
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|
|
|
|
|
[PubMed: 22785315]
|
|
|
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|
|
[Full Text: https://doi.org/10.1038/nature11181]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Silverstein, T. D., Johnson, R. E., Jain, R., Prakash, L., Prakash, S., Aggarwal, A. K.
|
|
<strong>Structural basis for the suppression of skin cancers by DNA polymerase eta.</strong>
|
|
Nature 465: 1039-1043, 2010.
|
|
|
|
|
|
[PubMed: 20577207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09104]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, D., Lippard, S. J.
|
|
<strong>Cellular processing of platinum anticancer drugs.</strong>
|
|
Nature Rev. Drug Discov. 4: 307-320, 2005.
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|
|
|
|
|
[PubMed: 15789122]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nrd1691]
|
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|
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</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Yamada, A., Masutani, C., Iwai, S., Hanaoka, F.
|
|
<strong>Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta.</strong>
|
|
Nucleic Acids Res. 28: 2473-2480, 2000.
|
|
|
|
|
|
[PubMed: 10871396]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/28.13.2473]
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Yuasa, M., Masutani, C., Eki, T., Hanaoka, F.
|
|
<strong>Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene.</strong>
|
|
Oncogene 19: 4721-4728, 2000.
|
|
|
|
|
|
[PubMed: 11032022]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.onc.1203842]
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</p>
|
|
</li>
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</ol>
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
</div>
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</div>
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<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 09/04/2012<br>George E. Tiller - updated : 12/1/2011<br>Ada Hamosh - updated : 8/17/2010<br>Patricia A. Hartz - updated : 1/24/2006<br>Victor A. McKusick - updated : 2/6/2002<br>Gary A. Bellus - updated : 4/11/2001<br>Victor A. McKusick - updated : 1/9/2001<br>Victor A. McKusick - updated : 9/6/2000<br>Ada Hamosh - updated : 8/1/2000<br>Ada Hamosh - updated : 6/9/2000<br>Ada Hamosh - updated : 7/9/1999
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Ada Hamosh : 7/8/1999
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carol : 09/28/2016<br>alopez : 09/04/2012<br>alopez : 12/5/2011<br>alopez : 12/5/2011<br>terry : 12/1/2011<br>alopez : 9/7/2011<br>alopez : 8/20/2010<br>terry : 8/17/2010<br>carol : 6/3/2009<br>terry : 5/20/2008<br>alopez : 11/28/2007<br>alopez : 11/28/2007<br>mgross : 2/21/2006<br>mgross : 2/2/2006<br>terry : 1/24/2006<br>carol : 8/13/2004<br>cwells : 11/7/2003<br>mgross : 2/11/2002<br>terry : 2/6/2002<br>cwells : 4/12/2001<br>cwells : 4/11/2001<br>mcapotos : 1/22/2001<br>mcapotos : 1/16/2001<br>terry : 1/9/2001<br>mcapotos : 9/6/2000<br>alopez : 9/1/2000<br>alopez : 8/2/2000<br>terry : 8/1/2000<br>alopez : 6/16/2000<br>terry : 6/9/2000<br>carol : 2/23/2000<br>carol : 2/23/2000<br>alopez : 11/23/1999<br>alopez : 10/13/1999<br>carol : 7/12/1999<br>terry : 7/9/1999<br>carol : 7/8/1999<br>carol : 7/8/1999
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