Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Dec;162(6):353-63.
doi: 10.1016/j.trsl.2013.05.003. Epub 2013 Jun 1.

Short telomeres: from dyskeratosis congenita to sporadic aplastic anemia and malignancy

Maria M Gramatges  1 , Alison A Bertuch
Affiliations
Review

Short telomeres: from dyskeratosis congenita to sporadic aplastic anemia and malignancy

Maria M Gramatges et al. Transl Res. 2013 Dec.

Abstract

Telomeres are DNA-protein structures that form a protective cap on chromosome ends. As such, they prevent the natural ends of linear chromosomes from being subjected to DNA repair activities that would result in telomere fusion, degradation, or recombination. Both the DNA and protein components of the telomere are required for this essential function, because insufficient telomeric DNA length, loss of the terminal telomeric DNA structure, or deficiency of key telomere-associated factors may elicit a DNA damage response and result in cellular senescence or apoptosis. In the setting of failed checkpoint mechanisms, such DNA-protein defects can also lead to genomic instability through telomere fusions or recombination. Thus, as shown in both model systems and in humans, defects in telomere biology are implicated in cellular and organismal aging as well as in tumorigenesis. Bone marrow failure and malignancy are 2 life-threatening disease manifestations in the inherited telomere biology disorder dyskeratosis congenita. We provide an overview of basic telomere structure and maintenance. We outline the telomere biology defects observed in dyskeratosis congenita, focusing on recent discoveries in this field. Last, we review the evidence of how telomere biology may impact sporadic aplastic anemia and the risk for various cancers.

Keywords: AML; CLL; CST; CTC1; CTC1/STN1/TEN1; DC; FA; FISH; Fanconi anemia; MDS; O/E; POT1; Q-PCR; RAP1; RTEL1; STN1; TEN1; TERC; TERF1 (TRF1)-interacting nuclear factor 2; TERT; TIN2; TIN2-interacting protein 1; TINF2; TPP1; TRF1; TRF1-interacting protein 2; TRF2; acute myeloid leukemia; base pairs; bp; chronic lymphocytic leukemia; conserved telomere maintenance component 1; dyskeratosis congenita; fluorescence in situ hybridization; myelodysplastic syndrome; odds over expected ratio; protection of telomeres 1; quantitative polymerase chain reaction; regulator of telomere elongation helicase 1; repressor/activator protein 1; suppressor of cdc13-1; telomerase RNA component; telomerase reverse transcriptase; telomeric pathway with STN1; telomeric repeat factor 1; telomeric repeat factor 2.

PubMed Disclaimer

Conflict of interest statement

All authors have read the journal's policy on conflicts of interest and have none to declare.

Figures

Figure 1
Figure 1
Factors influencing telomere length maintenance and associated with telomere biology disorders, such as DC. A. TCAB1 associates with telomerase, directing its trafficking through the Cajal body, which is required for its recruitment to telomeres. B. TERT, TERC and dyskerin (DKC1) are components of the telomerase holoenzyme. Mutations in these subunits impact telomerase activity and are associated with diseases in the telomere biology disorder spectrum. C. Shelterin associates with telomeric DNA, providing protection of the telomeric end and contributing to the regulation of telomerase. Shown here is only shelterin associated with the telomeric end, although it is also bound along the duplex telomeric tract. TIN2 is the only shelterin subunit that has been found to be mutated in DC or related disorders to date. D. The CST complex has been proposed to contribute in telomere maintenance with effects on telomerase recruitment as well as some aspects of DNA replication. Of the CST subunits, only CTC1 has been implicated in disease thus far. E. Mouse studies implicate the RTEL1 helicase in telomere replication and stability of the telomere t-loops. RTEL1 is the most recent DC-associated gene.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A. 1988;85:6622–6626. - PMC - PubMed
    1. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100–2110. - PubMed
    1. Stewart JA, Chaiken MF, Wang F, Price CM. Maintaining the end: roles of telomere proteins in end-protection, telomere replication and length regulation. Mutat Res. 2012;730:12–19. - PMC - PubMed
    1. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, et al. Mammalian telomeres end in a large duplex loop. Cell. 1999;97:503–514. - PubMed
    1. de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM, et al. Structure and variability of human chromosome ends. Mol Cell Biol. 1990;10:518–527. - PMC - PubMed

Publication types