期刊
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
卷 163, 期 -, 页码 109-119出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2021.03.007
关键词
PIKKs; DNA damage Signalling; Homologous recombination; Replication stress; Protein kinases; Regulation
资金
- Wellcome Trust [098412/Z/12/Z, 210658/Z/18/Z]
- Wellcome Trust [210658/Z/18/Z] Funding Source: Wellcome Trust
The maintenance of genome integrity is critical for cell survival and genetic information protection, in which ATM and ATR play key roles. While their roles are closely intertwined in response to double strand breaks, they diverge in the response to replication stress.
The maintenance of genome integrity is critical for the faithful replication of the genome during cell division and for protecting cells from accumulation of DNA damage, which if left unrepaired leads to a loss of genetic information, a breakdown in cell function and ultimately cell death and cancer. ATM and ATR are master kinases that are integral to homologous recombination-mediated repair of double strand breaks and preventing accumulation of dangerous DNA structures and genome instability during replication stress. While the roles of ATM and ATR are heavily intertwined in response to double strand breaks, their roles diverge in the response to replication stress. This review summarises our understanding of the players and their mode of actions in recruitment, activation and activity of ATM and ATR in response to DNA damage and replication stress and discusses how controlling localisation of these kinases and their activators allows them to orchestrate a stress-specific response. (C) 2021 Published by Elsevier Ltd.
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