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Curr Opin Cell Biol. 2007 Apr;19(2):238-45. Epub 2007 Feb 15.

DNA damage checkpoints: from initiation to recovery or adaptation.

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1
Department of Cell Cycle and Cancer, and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. jb@cancer.dk

Abstract

In response to diverse genotoxic stresses, cells activate DNA damage checkpoint pathways to protect genomic integrity and promote survival of the organism. Depending on DNA lesions and context, damaged cells with alarmed checkpoints can be eliminated by apoptosis or silenced by cellular senescence, or can survive and resume cell cycle progression upon checkpoint termination. Over the past two years a plethora of mechanistic studies have provided exciting insights into the biology and pathology of checkpoint initiation and signal propagation, and have revealed the various ways in which the response can be terminated: through recovery, adaptation or cancer-prone subversion. Such studies highlight the dynamic nature of these processes and help us to better understand the molecular basis, spatiotemporal orchestration and biological significance of the DNA damage response in normal and cancerous cells.

PMID:
17303408
DOI:
10.1016/j.ceb.2007.02.009
[Indexed for MEDLINE]
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