Cimprich Karlene A, Cortez David
Department of Chemical and Systems Biology, Stanford University School of Medicine, Clark Center, 318 Campus Drive, W350B, Stanford, California 94305-5441, USA.
Nat Rev Mol Cell Biol. 2008 Aug;9(8):616-27. doi: 10.1038/nrm2450. Epub 2008 Jul 2.
Genome maintenance is a constant concern for cells, and a coordinated response to DNA damage is required to maintain cellular viability and prevent disease. The ataxia-telangiectasia mutated (ATM) and ATM and RAD3-related (ATR) protein kinases act as master regulators of the DNA-damage response by signalling to control cell-cycle transitions, DNA replication, DNA repair and apoptosis. Recent studies have provided new insights into the mechanisms that control ATR activation, have helped to explain the overlapping but non-redundant activities of ATR and ATM in DNA-damage signalling, and have clarified the crucial functions of ATR in maintaining genome integrity.
基因组维护是细胞一直关注的问题,细胞需要对DNA损伤作出协调反应以维持细胞活力并预防疾病。共济失调毛细血管扩张症突变基因(ATM)以及ATM和RAD3相关蛋白激酶(ATR)作为DNA损伤反应的主要调节因子,通过发出信号来控制细胞周期转换、DNA复制、DNA修复和细胞凋亡。最近的研究为控制ATR激活的机制提供了新见解,有助于解释ATR和ATM在DNA损伤信号传导中的重叠但非冗余活性,并阐明了ATR在维持基因组完整性方面的关键功能。