DNA damage checkpoints in stem cells, ageing and cancer

被引：314
作者：
Sperka, Tobias
Wang, Jianwei
Rudolph, K. Lenhard [1 ]
机构：
[1] FLI, Leibniz Inst Age Res, D-07745 Jena, Germany
来源：
NATURE REVIEWS MOLECULAR CELL BIOLOGY | 2012年 / 13卷 / 09期
关键词：
HEMATOPOIETIC STEM; TELOMERE DYSFUNCTION; SELF-RENEWAL; SKELETAL-MUSCLE; LIFE-SPAN; CELLULAR SENESCENCE; GENOTOXIC STRESS; INTESTINAL CRYPT; LIMITED ROLE; P53;
D O I：
10.1038/nrm3420
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
引用
收藏
页码：579 / 590
页数：12
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