Document Detail


DNA damage checkpoints in stem cells, ageing and cancer.
MedLine Citation:
PMID:  22914294     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
DNA damage induces cell-intrinsic checkpoints, including p53 and retinoblastoma (RB), as well as upstream regulators (exonuclease 1 (EXO1), ataxia telangiectasia mutated (ATM), ATR, p16(INK4a) and p19(ARF)) and downstream targets (p21, PUMA (p53 upregulated modulator of apoptosis) and sestrins). Clearance of damaged cells by cell-intrinsic checkpoints suppresses carcinogenesis but as a downside may impair stem cell and tissue maintenance during ageing. Modulating the activity of DNA damage checkpoints can either accelerate or decelerate tissue ageing and age-related carcinogenesis. The outcome depends on cell-intrinsic and cell-extrinsic mechanisms that regulate the clearance of damaged cells and on the molecular context in ageing tissues, including the level of DNA damage accumulation itself.
Authors:
Tobias Sperka; Jianwei Wang; K Lenhard Rudolph
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature reviews. Molecular cell biology     Volume:  13     ISSN:  1471-0080     ISO Abbreviation:  Nat. Rev. Mol. Cell Biol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100962782     Medline TA:  Nat Rev Mol Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  579-90     Citation Subset:  IM    
Affiliation:
1] Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745 Jena, Germany, and Institute for Molecular Medicine, Ulm University, Germany. [2].
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