Berger N Daniel, Stanley Fintan K T, Moore Shaun, Goodarzi Aaron A
Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1
Philos Trans R Soc Lond B Biol Sci. 2017 Oct 5;372(1731). doi: 10.1098/rstb.2016.0283.
Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.
共济失调毛细血管扩张症突变基因(ATM)是一种丝氨酸/苏氨酸蛋白激酶,在DNA损伤反应中具有主要调节功能。在此过程中,ATM指挥一个复杂的生化网络,该网络能指示氧化性DNA损伤(包括危险的DNA双链断裂)的存在,并促进后续修复。在这里,我们综述了当前关于依赖ATM的染色质重塑和表观基因组改变的知识状态,这些改变是在存在DNA双链断裂和/或氧化应激的情况下维持基因组完整性所必需的。我们将特别关注ATM在复杂染色质环境中未解决的DNA双链断裂位点调节核小体间距的作用,以及ATM对维持哺乳动物中枢神经系统内细胞健康的影响。本文是主题为“DNA修复和信号传导中的染色质修饰剂和重塑剂”的特刊的一部分。