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<meta name="description" content="Mutations in TREX1 have been linked to a spectrum of human autoimmune diseases including Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus, and retinal vasculopathy and cerebral leukodystrophy. A common feature in these conditions is the frequent detectio …"><meta name="keywords" content="pmid:18805785, PMC2581595, doi:10.1074/jbc.M806155200, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Duane A Lehtinen, Scott Harvey, Fred W Perrino, Autoimmune Diseases / enzymology*, Autoimmune Diseases / genetics, DNA / metabolism*, Exodeoxyribonucleases / chemistry*, Exodeoxyribonucleases / genetics, Exodeoxyribonucleases / metabolism*, Humans, Models, Molecular, Mutation / genetics, Phosphoproteins / chemistry*, Phosphoproteins / genetics, Phosphoproteins / metabolism*, Protein Multimerization, Protein Structure, Quaternary, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/18805785/"><meta property="og:description" content="Mutations in TREX1 have been linked to a spectrum of human autoimmune diseases including Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus, and retinal vasculopathy and cerebral leukodystrophy. A common feature in these conditions is the frequent detectio …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/18805785/"><meta name="twitter:description" content="Mutations in TREX1 have been linked to a spectrum of human autoimmune diseases including Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus, and retinal vasculopathy and cerebral leukodystrophy. A common feature in these conditions is the frequent detectio …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18805785%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18805785%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 18805785 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 18805785"/>
|
||
<input type="hidden" name="email-subject-hash" value="dbcc9410f159654dbac1fbfa413c8adb4aef5cf177bab7347a4255c22d435538"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="18805785">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)56908-1"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=18805785&db=pubmed&nlmid=2985121R"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="18805785"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/18805785/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=18805785&db=pubmed&nlmid=2985121R"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="18805785"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/18805785/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/18805785/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="18805785" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18805785%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="TQwnUYECyToYUwGhYobVk0SSXo4vFNFHaDgsxO7Y8ubsOXM7BHOXO8owvsMHyod1"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title">
|
||
Display options
|
||
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2008 Nov 14;283(46):31649-56.</span>
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The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease
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The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease
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Mutations in TREX1 have been linked to a spectrum of human autoimmune diseases including Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus, and retinal vasculopathy and cerebral leukodystrophy. A common feature in these conditions is the frequent detection of antibodies to double-stranded DNA (dsDNA). TREX1 participates in a cell death process implicating this major 3' --> 5' exonuclease in genomic DNA degradation to minimize potential immune activation by persistent self DNA. The TREX1 D200N and D18N dominant heterozygous mutations were identified in AGS and FCL, respectively. TREX1 enzymes containing the D200N and D18N mutations were compared using nicked dsDNA and single-stranded DNA (ssDNA) degradation assays. The TREX1WT/D200N and TREX1WT/D18N heterodimers are completely deficient at degrading dsDNA and degrade ssDNA at an expected approximately 2-fold lower rate than TREX1WT enzyme. Further, the D200N- and D18N-containing TREX1 homo- and heterodimers inhibit the dsDNA degradation activity of TREX1WT enzyme, providing a likely explanation for the dominant phenotype of these TREX1 mutant alleles in AGS and FCL. By comparison, the TREX1 R114H homozygous mutation causes AGS and is found as a heterozygous mutation in systemic lupus erythematosus. The TREX1R114H/R114H homodimer has dysfunctional dsDNA and ssDNA degradation activities and does not detectibly inhibit the TREX1WT enzyme, whereas the TREX1WT/R114H heterodimer has a functional dsDNA degradation activity, supporting the recessive genetics of TREX1 R114H in AGS. The dysfunctional dsDNA degradation activities of these disease-related TREX1 mutants could account for persistent dsDNA from dying cells leading to an aberrant immune response in these clinically related disorders.
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<div class="figure-caption-contents"><b> The TREX1 dimer with bound… </b></div>
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<div class="figure-caption-contents"><b> The TREX1 dimer with bound ssDNA. </b> The TREX1 protomer backbones ( <i> orange </i> and…</div>
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FIGURE 1.
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<div class="figure-caption-contents"><b>The TREX1 dimer with bound ssDNA.</b> The TREX1 protomer backbones
|
||
(<i>orange</i> and <i>green</i>) are shown. The Asp-18 (<i>blue</i>),
|
||
Asp-200 (<i>magenta</i>), Arg-114 (<i>red</i>), and Arg-128
|
||
(<i>gray</i>) residue side chains (shown as <i>sticks</i>) are indicated
|
||
in each of the TREX1 protomers. The active sites (<i>highlighted
|
||
circles</i>) and dimer interface (<i>brackets</i>) are indicated. The
|
||
Ca<sup>2+</sup> divalent ions (<i>cyan</i>) coordinated by D18 and D200
|
||
(<i>black dotted lines</i>) and 4-mer ssDNA (as <i>sticks</i>) are shown
|
||
bound in the active sites. The β3 strands and α4 helices at the
|
||
dimer interface are shown as <i>cartoons</i>. The hydrogen bonding at the
|
||
dimer interface (<i>black dotted lines</i>) is indicated. The Arg-114 of
|
||
each protomer hydrogen bonds to the backbone carbonyl oxygens of Gln-98 and
|
||
Arg-99 in the opposing protomer. The figure was prepared using the program
|
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PyMol (Delano Scientific).</div>
|
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data-image-height="515"
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data-image-alt="FIGURE 2."
|
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|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-1"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/aa15ab68912b/zbc0500857070002.gif"
|
||
alt="FIGURE 2." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="475">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="515">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 2. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The ssDNA exonuclease activities of… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 2. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The ssDNA exonuclease activities of TREX1 <sup> WT </sup> and D200N variants. </b> Standard exonuclease reactions…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 2.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>The ssDNA exonuclease activities of TREX1<sup>WT</sup> and D200N
|
||
variants.</b> Standard exonuclease reactions (30 μl) were prepared with a
|
||
fluorescein-labeled 30-mer oligonucleotide and dilutions of the recombinant
|
||
wild type (TREX1<sup>WT</sup>), mutant (TREX1<sup>D200N/D200N</sup>)
|
||
homodimer, and (TREX1<sup>WT/D200N</sup>) heterodimer were prepared at 10
|
||
times the final concentrations. Samples (3 μl) containing the TREX1 enzymes
|
||
to yield the final indicated concentrations were added to reactions. The
|
||
incubations were 20 min at 25 °C. The reaction products were subjected to
|
||
electrophoresis on 23% urea-polyacrylamide gels (<i>A</i>) and quantified
|
||
(<i>B</i>) as described under “Experimental Procedures.” The
|
||
position of migration of the 30-mer is indicated. Relative activities of
|
||
TREX1<sup>D200N/D200N</sup> and TREX1<sup>WT/D200N</sup> are compared with
|
||
TREX1<sup>WT</sup> dimers. The relative activity was calculated as relative
|
||
activity = 100 × [(fmol of dNMP released/s/fmol of mutant enzyme)/(fmol
|
||
of dNMP released/s/fmol WT enzyme)].</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="2"
|
||
data-label-slug="figure-3">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/9f33b99a25f2/zbc0500857070003.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-2"
|
||
role="button"
|
||
data-image-width="475"
|
||
data-image-height="773"
|
||
data-image-alt="FIGURE 3."
|
||
data-pmc-id="PMC2581595"
|
||
data-figure-id="fig3">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-2"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/d9e9f225feb0/zbc0500857070003.gif"
|
||
alt="FIGURE 3." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="475">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="773">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 3. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The ssDNA exonuclease activities of… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 3. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The ssDNA exonuclease activities of TREX1 <sup> WT </sup> and R114H variants. </b> The standard exonuclease…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 3.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>The ssDNA exonuclease activities of TREX1<sup>WT</sup> and R114H
|
||
variants.</b> The standard exonuclease reactions (30 μl) were prepared with
|
||
a fluorescein-labeled 30-mer oligonucleotide, and dilutions of the recombinant
|
||
wild type (TREX1<sup>WT</sup>), mutant (TREX1<sup>R114H/R114H</sup>)
|
||
homodimer, and (TREX1<sup>WT/R114H</sup>) heterodimer were prepared at 10
|
||
times the final concentrations. Samples (3 μl) containing the TREX1 enzymes
|
||
to yield the final indicated concentrations were added to reactions. The
|
||
incubations were 20 min at 25 °C. The reaction products were subjected to
|
||
electrophoresis on 23% urea-polyacrylamide gels (<i>A</i>) and quantified
|
||
(<i>B</i>) as described under “Experimental Procedures.” The
|
||
position of migration of the 30-mer is indicated. Relative activities of
|
||
TREX1<sup>R114H/R114H</sup> and TREX1<sup>WT/R114H</sup> are compared with
|
||
TREX1<sup>WT</sup> dimers. The relative activity was calculated as relative
|
||
activity = 100 × [(fmol of dNMP released/s/fmol of mutant enzyme)/(fmol
|
||
of dNMP released/s/fmol WT enzyme)].</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="3"
|
||
data-label-slug="figure-4">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/41c36237d94a/zbc0500857070004.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-3"
|
||
role="button"
|
||
data-image-width="475"
|
||
data-image-height="639"
|
||
data-image-alt="FIGURE 4."
|
||
data-pmc-id="PMC2581595"
|
||
data-figure-id="fig4">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/96f489018d61/zbc0500857070004.gif"
|
||
alt="FIGURE 4." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="475">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="639">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 4. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 3′ exonuclease has… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 4. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 3′ exonuclease has dsDNA degradation activity. </b> The supercoiled dsDNA plasmids 1…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 4.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>The TREX1 3′ exonuclease has dsDNA degradation activity.</b> The
|
||
supercoiled dsDNA plasmids 1 (<i>A, lane 2</i>) and 2 (<i>B, lane 8</i>)
|
||
were nicked by incubating with Nt.BbvCI restriction enzyme (<i>A, lane
|
||
3</i>; and <i>B, lane 9</i>) and purified as described under
|
||
“Experimental Procedures.” The plasmid 2 was linearized by
|
||
incubating with EcoRI (<i>C, lane 2</i>) or SacI (<i>D, lane 8</i>) and
|
||
purified. Exonuclease time course reactions (100 μl) were prepared
|
||
containing nicked dsDNA plasmid 1 (<i>A</i>) or 2 (<i>B</i>) or linearized
|
||
dsDNA plasmid 2 (<i>C</i> and <i>D</i>) and 7.6 n<sc>m</sc>
|
||
TREX1<sup>WT</sup>. The samples (20 μl) were removed after incubation for
|
||
the indicated times (<i>A, lanes 4–7</i>; and <i>B, lanes
|
||
10–13</i>). The reaction products were subjected to electrophoresis on
|
||
agarose gels, and the amounts of dNMP excised by TREX1<sup>WT</sup> were
|
||
estimated as described under “Experimental Procedures.” The
|
||
positions of migration of Form I supercoiled dsDNA (<i>dsDNA</i>), Form II
|
||
nicked dsDNA (<i>Nicked dsDNA</i>), Form III linear dsDNA (<i>linear
|
||
dsDNA</i>), and circular ssDNA (<i>ssDNA</i>) are indicated. <i>Lane
|
||
1</i> contains the 1-kb ladder (Invitrogen).</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="4"
|
||
data-label-slug="figure-5">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/fc4aabf37bc1/zbc0500857070005.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-4"
|
||
role="button"
|
||
data-image-width="448"
|
||
data-image-height="143"
|
||
data-image-alt="FIGURE 5."
|
||
data-pmc-id="PMC2581595"
|
||
data-figure-id="fig5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/4573b0009a7a/zbc0500857070005.gif"
|
||
alt="FIGURE 5." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="448">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="143">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 <sup> WT/D200N </sup> and TREX1… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 <sup> WT/D200N </sup> and TREX1 <sup> WT/D18N </sup> heterodimers have defective dsDNA degradation activities. </b> The…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 5.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>The TREX1<sup>WT/D200N</sup> and TREX1<sup>WT/D18N</sup> heterodimers
|
||
have defective dsDNA degradation activities.</b> The exonuclease reactions (20
|
||
μl) were prepared containing nicked dsDNA plasmid 1 (10 μg/ml = 1.6
|
||
n<sc>m</sc> nicks) and no enzyme (<i>lanes 2, 8</i>, and <i>14</i>) or
|
||
the indicated increased concentrations (in n<sc>m</sc>) of
|
||
TREX1<sup>WT</sup> (<i>lanes 3–7</i>), TREX1<sup>WT/D200N</sup>
|
||
(<i>lanes 9–13</i>), and TREX1<sup>WT/D18N</sup> (<i>lanes
|
||
15–19</i>). The reactions were 30 min, and the products were subjected
|
||
to electrophoresis on agarose gels. <i>Lane 1</i> (<i>ds</i>) contains the
|
||
supercoiled dsDNA plasmid 1. The positions of migration of Form I supercoiled
|
||
dsDNA (<i>dsDNA</i>), Form II nicked dsDNA (<i>Nicked dsDNA</i>), and
|
||
circular ssDNA (<i>ssDNA</i>) are indicated.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="5"
|
||
data-label-slug="figure-6">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/02869dc7696b/zbc0500857070006.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-5"
|
||
role="button"
|
||
data-image-width="475"
|
||
data-image-height="517"
|
||
data-image-alt="FIGURE 6."
|
||
data-pmc-id="PMC2581595"
|
||
data-figure-id="fig6">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/79a4950890ce/zbc0500857070006.gif"
|
||
alt="FIGURE 6." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="475">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="517">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 6. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The D200N- and D18N-containing TREX1… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 6. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The D200N- and D18N-containing TREX1 mutant enzymes inhibit the TREX1 <sup> WT </sup> dsDNA degradation… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 6.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>The D200N- and D18N-containing TREX1 mutant enzymes inhibit the
|
||
TREX1<sup>WT</sup> dsDNA degradation activity.</b> Exonuclease reactions (20
|
||
μl) were prepared containing nicked dsDNA plasmid 1 (10 μg/ml = 1.6
|
||
n<sc>m</sc> nicks) and no enzyme (<i>A</i> and <i>B, lane 2</i>), the
|
||
indicated concentration of TREX1<sup>WT</sup> only (<i>A</i> and <i>B, lane
|
||
3</i>), or a mixture of TREX1<sup>WT</sup> with the indicated increased
|
||
concentrations of TREX1<sup>D200N/D200N</sup> (<i>A, lanes 4–8</i>),
|
||
TREX1<sup>WT/D200N</sup> (<i>A, lanes 9–13</i>),
|
||
TREX1<sup>D18N/D18N</sup> (<i>B, lanes 4–8</i>), and
|
||
TREX1<sup>WT/D18N</sup> (<i>lanes 9–13</i>). The reactions were 30
|
||
min, and the products were subjected to electrophoresis on agarose gels.
|
||
<i>Lane 1</i> contains the supercoiled dsDNA plasmid 1. The positions of
|
||
migration of Form I supercoiled dsDNA (<i>dsDNA</i>), Form II nicked dsDNA
|
||
(<i>Nicked dsDNA</i>), and circular ssDNA (<i>ssDNA</i>) are
|
||
indicated.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="6"
|
||
data-label-slug="figure-7">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/13fb548899af/zbc0500857070007.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-6"
|
||
role="button"
|
||
data-image-width="416"
|
||
data-image-height="233"
|
||
data-image-alt="FIGURE 7."
|
||
data-pmc-id="PMC2581595"
|
||
data-figure-id="fig7">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-6"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/d43f5e0a1e42/zbc0500857070007.gif"
|
||
alt="FIGURE 7." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="416">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="233">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 7. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 <sup> R114H/R114H </sup> dsDNA degradation… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 7. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 <sup> R114H/R114H </sup> dsDNA degradation activity is more dysfunctional than the ssDNA exonuclease… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 7.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>The TREX1<sup>R114H/R114H</sup> dsDNA degradation activity is more
|
||
dysfunctional than the ssDNA exonuclease activity.</b> Exonuclease time course
|
||
reactions (200 μl) were prepared containing nicked dsDNA plasmid 1 (10
|
||
μg/ml = 1.6 n<sc>m</sc> nicks) and 7.6 n<sc>m</sc> TREX1<sup>WT</sup>
|
||
(<i>A</i>) and 260 n<sc>m</sc> TREX1<sup>R114H/R114H</sup> (<i>B</i>).
|
||
The samples (20 μl) were removed prior to enzyme addition (<i>lanes 2</i>
|
||
and <i>5</i>) and after incubation for the indicated times (<i>A, lanes
|
||
3</i> and <i>4</i>; and <i>B, lanes 7–12</i>). The reaction
|
||
products were subjected to electrophoresis on agarose gels. <i>Lanes 1</i>
|
||
and <i>5</i> (<i>ds</i>) contain the supercoiled dsDNA plasmid 1. The
|
||
positions of migration of Form I supercoiled dsDNA (<i>dsDNA</i>), Form II
|
||
nicked dsDNA (<i>Nicked dsDNA</i>), and circular ssDNA (<i>ssDNA</i>) are
|
||
indicated.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
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|
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itemscope itemtype="http://schema.org/ImageObject"
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data-label-slug="figure-8">
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|
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aria-describedby="figure-caption-7"
|
||
role="button"
|
||
data-image-width="475"
|
||
data-image-height="228"
|
||
data-image-alt="FIGURE 8."
|
||
data-pmc-id="PMC2581595"
|
||
data-figure-id="fig8">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-7"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a7a/2581595/ea8971b0496a/zbc0500857070008.gif"
|
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|
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|
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|
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<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="475">
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<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="228">
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|
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|
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<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 8. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 <sup> R114H/R114H </sup> and TREX1… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 8. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> The TREX1 <sup> R114H/R114H </sup> and TREX1 <sup> WT/R114H </sup> enzymes do not inhibit the TREX1M <sup> WT… </sup> </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 8.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>The TREX1<sup>R114H/R114H</sup> and TREX1<sup>WT/R114H</sup> enzymes do
|
||
not inhibit the TREX1M<sup>WT</sup> dsDNA degradation activity.</b>
|
||
Exonuclease reactions (20 μl) were prepared containing nicked dsDNA plasmid
|
||
1 (10 μg/ml = 1.6 n<sc>m</sc> nicks) and no enzyme (<i>lane 2</i>), the
|
||
indicated concentration of TREX1<sup>WT</sup> only (<i>lane 3</i>), or a
|
||
mixture of TREX1<sup>WT</sup> with the indicated increased concentrations of
|
||
TREX1<sup>R114H/R114H</sup> (<i>lanes 4–8</i>), and
|
||
TREX1<sup>WT/R114H</sup> (<i>lanes 9–13</i>). The reactions were 30
|
||
min, and the products were subjected to electrophoresis on agarose gels.
|
||
<i>Lane 1</i> contains the supercoiled dsDNA plasmid 1. The positions of
|
||
migration of Form I supercoiled dsDNA (<i>dsDNA</i>), Form II nicked dsDNA
|
||
(<i>Nicked dsDNA</i>), and circular ssDNA (<i>ssDNA</i>) are
|
||
indicated.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
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|
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aria-label="Toggle dropdown menu for keyword Autoimmune Diseases / enzymology*"
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aria-expanded="false"
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Autoimmune Diseases / enzymology*
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aria-label="Dropdown menu for keyword Autoimmune Diseases / enzymology*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Autoimmune+Diseases%2Fenzymology%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Autoimmune+Diseases%2Fenzymology%22%5BMAJR%5D&sort=date&sort_order=desc"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Autoimmune Diseases / genetics
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aria-label="Dropdown menu for keyword Autoimmune Diseases / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Autoimmune+Diseases%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Autoimmune+Diseases%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Dropdown menu for keyword DNA / metabolism*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Exodeoxyribonucleases / metabolism*
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aria-label="Dropdown menu for keyword Exodeoxyribonucleases / metabolism*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Exodeoxyribonucleases%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Exodeoxyribonucleases%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
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aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Models, Molecular
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aria-label="Dropdown menu for keyword Models, Molecular"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Mutation / genetics
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aria-label="Dropdown menu for keyword Mutation / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Phosphoproteins / chemistry*
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Phosphoproteins/genetics"[MeSH]"
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
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|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Phosphoproteins"
|
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Phosphoproteins / metabolism*"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Phosphoproteins / metabolism*
|
||
</button><div id="keyword-actions-mesh-terms-major-11"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
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aria-label="Dropdown menu for keyword Phosphoproteins / metabolism*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Phosphoproteins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Phosphoproteins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Phosphoproteins/metabolism"[MAJR]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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|
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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data-search-term=""Phosphoproteins/metabolism"[MAJR]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Protein Multimerization"
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aria-expanded="false"
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data-pinger-ignore>
|
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Protein Multimerization
|
||
</button><div id="keyword-actions-mesh-terms-12"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Protein Multimerization"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Protein+Multimerization%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Protein Structure, Quaternary"
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Protein Structure, Quaternary
|
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</button><div id="keyword-actions-mesh-terms-13"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Protein Structure, Quaternary"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li></ul>
|
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</div>
|
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|
||
|
||
|
||
|
||
|
||
<div id="substances" class="substances keywords-section">
|
||
<h2 class="title">
|
||
Substances
|
||
</h2>
|
||
|
||
<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Phosphoproteins"
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tabindex="0"
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aria-expanded="false"
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Phosphoproteins
|
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</button><div id="keyword-actions-substances-0"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Phosphoproteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Phosphoproteins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Phosphoproteins%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Phosphoproteins"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword DNA"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-1"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
||
DNA
|
||
</button><div id="keyword-actions-substances-1"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
||
aria-label="Dropdown menu for keyword DNA"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22DNA%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22DNA%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="DNA"[nm]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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data-ga-label="DNA">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
|
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data-search-term=""DNA"[nm]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""DNA"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Exodeoxyribonucleases"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-2"
|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
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Exodeoxyribonucleases
|
||
</button><div id="keyword-actions-substances-2"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
||
aria-label="Dropdown menu for keyword Exodeoxyribonucleases"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Exodeoxyribonucleases%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Exodeoxyribonucleases%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Exodeoxyribonucleases"[nm]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Exodeoxyribonucleases%22"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Exodeoxyribonucleases"[nm]"
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data-ga-category="search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword three prime repair exonuclease 1"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-3"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
three prime repair exonuclease 1
|
||
</button><div id="keyword-actions-substances-3"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
||
aria-label="Dropdown menu for keyword three prime repair exonuclease 1"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22three+prime+repair+exonuclease+1%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22three+prime+repair+exonuclease+1%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="three prime repair exonuclease 1"[nm]"
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Search in PubMed
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|
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22three+prime+repair+exonuclease+1%22"
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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role="button"
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data-search-term=""three prime repair exonuclease 1"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""three prime repair exonuclease 1"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div id="related-links" class="related-links">
|
||
<h2 class="title">
|
||
Related information
|
||
</h2>
|
||
|
||
<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&from_uid=18805785"
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=1">
|
||
Cited in Books
|
||
</a></li><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&from_uid=18805785"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=2">
|
||
ClinVar
|
||
</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&from_uid=18805785"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=3">
|
||
Gene
|
||
</a></li><li><a title="Link to Gene for the GeneRIF subcategory" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene_rif&from_uid=18805785"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=4">
|
||
Gene (GeneRIF)
|
||
</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=18805785"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=5">
|
||
MedGen
|
||
</a></li><li><a title="Related records in MedGen based on citations in GeneReviews and Medical Genetics Summaries" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen_bookshelf_cited&from_uid=18805785"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=6">
|
||
MedGen (Bookshelf cited)
|
||
</a></li><li><a title="OMIM (cited) Links" href="https://www.ncbi.nlm.nih.gov/omim?linkname=pubmed_omim_cited&from_uid=18805785"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=7">
|
||
OMIM (cited)
|
||
</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=18805785"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=8">
|
||
Protein (RefSeq)
|
||
</a></li><li><a title="Related PubChem Compound via MeSH" href="https://www.ncbi.nlm.nih.gov/pccompound?linkname=pubmed_pccompound_mesh&from_uid=18805785"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=9">
|
||
PubChem Compound (MeSH Keyword)
|
||
</a></li><li><a title="PubMed to SNP links" href="https://www.ncbi.nlm.nih.gov/snp?linkname=pubmed_snp&from_uid=18805785"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18805785&ordinalpos=1&linkpos=10">
|
||
SNP
|
||
</a></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="grants" class="grants">
|
||
<h2 class="title">
|
||
Grants and funding
|
||
</h2>
|
||
<div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a
|
||
title="All articles for grant GM069962/GM/NIGMS NIH HHS/United States"
|
||
href="/?term=GM069962%2FGM%2FNIGMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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ref="linksrc=grant_link"
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>
|
||
GM069962/GM/NIGMS NIH HHS/United States
|
||
</a></li></ul></div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="linkout" class="linkout">
|
||
<h2 class="title">
|
||
LinkOut - more resources
|
||
</h2>
|
||
|
||
<ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)56908-1"
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target="_blank"
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data-ga-label="Elsevier Science"
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Elsevier Science
|
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</a></li><li><a
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href="https://europepmc.org/abstract/MED/18805785"
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target="_blank"
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Europe PubMed Central
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