| Dyskerin, telomerase and the DNA damage response. | |
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MedLine Citation:
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PMID: 19106610 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The bone marrow failure syndrome Dyskeratosis congenita (DC), though rare, has attracted a great deal of attention in the last few years because it is caused by mutations in genes whose products are involved in telomere maintenance. The disease presents with a variety of features that can all be due to failure of tissues that require constant renewal via stem cell activity. It is thought this is caused by defects in telomere maintenance leading eventually to cell cycle arrest or cell death caused by critically short telomeres. The most common form of DC is the X-linked form caused by mutations in DKC1 encoding the nucleolar protein, dyskerin. We recently reported a mouse model of the X-linked form of the disease in which females heterozygous for a mutation that copies a human pathogenic mutation showed a growth disadvantage in cells expressing the mutant dyskerin. This growth disadvantage, which was associated with an enhanced DNA damage response, was dependent on telomerase but appeared to be independent of telomere shortening. Here we discuss these results in terms of the role of dyskerin in telomere maintenance and the possible role that the DNA damage response plays in the pathogenesis of DC. |
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Authors:
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BaiWei Gu; Monica Bessler; Philip J Mason |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2009-01-24 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 8 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-22 Completed Date: 2009-02-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 6-10 Citation Subset: IM |
Affiliation:
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Division of Hematology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle Proteins / genetics, metabolism* DNA Damage* Dyskeratosis Congenita / genetics, pathology Genetic Diseases, X-Linked / pathology Humans Mutation / genetics Telomerase / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL 04008/HL/NHLBI NIH HHS; R01 CA 106995/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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