Wilson Marcus D, Durocher Daniel
Macromolecular Machines Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.
Philos Trans R Soc Lond B Biol Sci. 2017 Oct 5;372(1731). doi: 10.1098/rstb.2016.0280.
DNA double-strand breaks (DSBs) are DNA lesions that must be accurately repaired in order to preserve genomic integrity and cellular viability. The response to DSBs reshapes the local chromatin environment and is largely orchestrated by the deposition, removal and detection of a complex set of chromatin-associated post-translational modifications. In particular, the nucleosome acts as a central signalling hub and landing platform in this process by organizing the recruitment of repair and signalling factors, while at the same time coordinating repair with other DNA-based cellular processes. While current research has provided a descriptive overview of which histone marks affect DSB repair, we are only beginning to understand how these marks are interpreted to foster an efficient DSB response. Here we review how the modified chromatin surrounding DSBs is read, with a focus on the insights gleaned from structural and biochemical studies.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.
DNA双链断裂(DSBs)是一种DNA损伤,为了保持基因组完整性和细胞活力,必须对其进行精确修复。对DSBs的反应重塑了局部染色质环境,并且在很大程度上是由一组复杂的与染色质相关的翻译后修饰的沉积、去除和检测来精心安排的。特别是,核小体在这个过程中作为一个核心信号枢纽和着陆平台,通过组织修复和信号因子的募集,同时协调修复与其他基于DNA的细胞过程。虽然目前的研究已经对哪些组蛋白标记影响DSB修复进行了描述性概述,但我们才刚刚开始了解这些标记是如何被解读以促进有效的DSB反应的。在这里,我们回顾了围绕DSBs的修饰染色质是如何被识别的,重点是从结构和生化研究中获得的见解。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。