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Nat Rev Mol Cell Biol. 2012 Sep;13(9):579-90. doi: 10.1038/nrm3420.

DNA damage checkpoints in stem cells, ageing and cancer.

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  • 1Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstr. 11, 07745 Jena, Germany.

Abstract

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.

PMID:
22914294
[PubMed - indexed for MEDLINE]
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