Progress in Biophysics and Molecular Biology ( IF 3.8 ) Pub Date : 2021-04-20 , DOI: 10.1016/j.pbiomolbio.2021.03.007 Rhys M Williams 1 , Xiaodong Zhang 1
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.
中文翻译:
ATM 和 ATR 在 DNA 双链断裂和复制应激中的作用
维持基因组完整性对于细胞分裂过程中基因组的忠实复制和保护细胞免受 DNA 损伤的积累至关重要,如果不修复会导致遗传信息丢失、细胞功能崩溃并最终导致细胞死亡和癌症. ATM 和 ATR 是主激酶,它们对于同源重组介导的双链断裂修复和防止复制压力期间危险 DNA 结构的积累和基因组不稳定性是不可或缺的。虽然 ATM 和 ATR 的作用在应对双链断裂时紧密交织在一起,但它们的作用在对复制压力的反应中却存在分歧。这篇评论总结了我们对球员的理解以及他们在招募中的行动方式,