Division of Nephrology, Department of Medicine, McMaster University; Father Sean O'Sullivan Research Institute; and the Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
Histol Histopathol. 2013 Dec;28(12):1547-54. doi: 10.14670/HH-28.1547. Epub 2013 Jul 9.
DNA damage response (DDR) is the critical surveillance mechanism in maintaining genome integrity. The mechanism activates checkpoints to prevent cell cycle progression in the presence of DNA lesions, and mediates lesion repair. DDR is coordinated by three apical PI3 kinase related kinases (PIKKs), including ataxia-telangiectasia mutated (ATM), ATM- and Rad3-related (ATR), and DNA-PKcs (the catalytic subunit of the DNA dependent protein kinase). These kinases are activated in response to specific DNA damage or lesions, resulting in checkpoint activation and DNA lesion repair. While it is clear that the pathways of ATM, ATR, and DNA-PK are the core components of DDR, there is accumulating evidence revealing the involvement of other cellular pathways in regulating DDR; this is in line with the concept that in addition to being a nuclear event DDR is also a cellular process. One of these pathways is the extracellular signal-regulated kinase (ERK) MAPK (mitogen-activated protein kinase) pathway. ERK is a converging point of multiple signal transduction pathways involved in cell proliferation, differentiation, and apoptosis. Adding to this list of pathways is the recent development of ERK in DDR. The ERK kinases (ERK1 and ERK2) contribute to the proper execution of DDR in terms of checkpoint activation and the repair of DNA lesions. This review summarizes the contributions of ERK to DDR with emphasis on the relationship of ERK kinases with the activation of ATM, ATR, and DNA-PKcs.
DNA 损伤反应 (DDR) 是维持基因组完整性的关键监控机制。该机制激活检查点，以防止在存在 DNA 损伤的情况下细胞周期进程，并介导损伤修复。DDR 由三个顶端 PI3 激酶相关激酶 (PIKKs) 协调，包括共济失调毛细血管扩张症突变 (ATM)、ATM 和 Rad3 相关 (ATR) 和 DNA 依赖性蛋白激酶 (DNA-PKcs)（DNA 依赖蛋白激酶的催化亚基）。这些激酶在响应特定的 DNA 损伤或损伤时被激活，导致检查点激活和 DNA 损伤修复。虽然 ATM、ATR 和 DNA-PK 的途径显然是 DDR 的核心组成部分，但越来越多的证据表明其他细胞途径参与调节 DDR；这符合除了是核事件之外，DDR 也是一个细胞过程的概念。其中一条途径是细胞外信号调节激酶 (ERK) MAPK（丝裂原激活蛋白激酶）途径。ERK 是参与细胞增殖、分化和凋亡的多个信号转导途径的汇聚点。ERK 在 DDR 中的新发展增加了这一途径列表。ERK 激酶 (ERK1 和 ERK2) 有助于适当执行 DDR，包括检查点激活和 DNA 损伤修复。这篇综述总结了 ERK 对 DDR 的贡献，重点介绍了 ERK 激酶与 ATM、ATR 和 DNA-PKcs 激活的关系。
