Unidad de Investigacion, Hospital Universitario de Canarias, Tenerife, Spain.
Front Biosci (Landmark Ed). 2010 Jun 1;15(3):840-53. doi: 10.2741/3649.
Cell cycle checkpoints maintain genomic integrity by delaying cell division in the presence of DNA damage or replication problems. A crucial player in this process is the ATR kinase. The rapid localisation of ATR to sites of genotoxic stress and the central role of this kinase in the checkpoint response lead to the suggestion that ATR functions as a sensor of DNA lesions. After activation, ATR phosphorylates and activates the effector kinase Chk1, thereby causing an inhibition in cell cycle progression. However, this would not be possible without the existence of many other proteins operating in this pathway. Here we review current progress in our understanding of the regulatory factors involved in the ATR-mediated checkpoint response, as well as resumption of cell cycle progression upon repair of the damage, thereby focussing on the mechanisms in mammalian cells.
细胞周期检查点通过在存在 DNA 损伤或复制问题时延迟细胞分裂来维持基因组完整性。在这个过程中，ATR 激酶是一个关键的参与者。ATR 迅速定位于遗传毒性应激部位，以及该激酶在检查点反应中的核心作用，使得 ATR 作为 DNA 损伤传感器的功能得到了提示。ATR 被激活后，磷酸化并激活效应激酶 Chk1，从而导致细胞周期进程的抑制。然而，如果没有许多其他在这个途径中起作用的蛋白质的存在，这是不可能的。在这里，我们综述了目前对 ATR 介导的检查点反应中涉及的调节因子的理解进展，以及在修复损伤后细胞周期进程的恢复，从而聚焦于哺乳动物细胞中的机制。
