Section of Structural and Synthetic Biology, Department of Infectious Disease, Imperial College London, London, SW7 2AZ, UK.
Section of Structural and Synthetic Biology, Department of Infectious Disease, Imperial College London, London, SW7 2AZ, UK.
Prog Biophys Mol Biol. 2021 Aug;163:109-119. doi: 10.1016/j.pbiomolbio.2021.03.007. Epub 2021 Apr 20.
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.
基因组完整性的维持对于细胞分裂过程中基因组的忠实复制以及防止细胞中 DNA 损伤的积累至关重要，如果这些损伤得不到修复，就会导致遗传信息的丢失、细胞功能的崩溃，最终导致细胞死亡和癌症。ATM 和 ATR 是关键的激酶，它们参与同源重组介导的双链断裂修复，并防止在复制应激过程中危险的 DNA 结构和基因组不稳定性的积累。虽然 ATM 和 ATR 在响应双链断裂时的作用紧密交织，但它们在响应复制应激时的作用有所不同。本文综述了我们对这些蛋白及其作用模式的理解，包括它们在招募、激活和活性方面的作用，以响应 DNA 损伤和复制应激，并讨论了如何控制这些激酶及其激活剂的定位，使它们能够协调特定于应激的反应。
