Yan Shan, Sorrell Melanie, Berman Zachary
Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC, 28223, USA,
Cell Mol Life Sci. 2014 Oct;71(20):3951-67. doi: 10.1007/s00018-014-1666-4. Epub 2014 Jun 20.
To maintain genome stability, cells have evolved various DNA repair pathways to deal with oxidative DNA damage. DNA damage response (DDR) pathways, including ATM-Chk2 and ATR-Chk1 checkpoints, are also activated in oxidative stress to coordinate DNA repair, cell cycle progression, transcription, apoptosis, and senescence. Several studies demonstrate that DDR pathways can regulate DNA repair pathways. On the other hand, accumulating evidence suggests that DNA repair pathways may modulate DDR pathway activation as well. In this review, we summarize our current understanding of how various DNA repair and DDR pathways are activated in response to oxidative DNA damage primarily from studies in eukaryotes. In particular, we analyze the functional interplay between DNA repair and DDR pathways in oxidative stress. A better understanding of cellular response to oxidative stress may provide novel avenues of treating human diseases, such as cancer and neurodegenerative disorders.
为维持基因组稳定性,细胞进化出多种DNA修复途径来应对氧化性DNA损伤。DNA损伤应答(DDR)途径,包括ATM-Chk2和ATR-Chk1检查点,在氧化应激中也会被激活,以协调DNA修复、细胞周期进程、转录、凋亡和衰老。多项研究表明,DDR途径可调节DNA修复途径。另一方面,越来越多的证据表明,DNA修复途径也可能调节DDR途径的激活。在本综述中,我们主要根据真核生物的研究总结了目前对各种DNA修复和DDR途径如何响应氧化性DNA损伤而被激活的理解。特别是,我们分析了氧化应激中DNA修复和DDR途径之间的功能相互作用。更好地理解细胞对氧化应激的反应可能为治疗人类疾病,如癌症和神经退行性疾病提供新途径。