Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures

作者：Thomas Clouaire, Vincent Rocher, Anahita Lashgari, Coline Arnould, Marion Aguirrebengoa, Anna Biernacka, Magdalena Skrzypczak, François Aymard, Bernard Fongang, Norbert Dojer, Jason S. Iacovoni, Maga Rowicka, Krzysztof Ginalski, Jacques Côté, Gaëlle Legube · 发表于：Molecular Cell · 年份：2018 · DOI：10.1016/j.molcel.2018.08.020 · 被引用次数：323 · 研究领域：DNA Repair Mechanisms、Genomics and Chromatin Dynamics、CRISPR and Genetic Engineering

Double-strand breaks (DSBs) are extremely detrimental DNA lesions that can lead to cancer-driving mutations and translocations. Non-homologous end joining (NHEJ) and homologous recombination (HR) represent the two main repair pathways operating in the context of chromatin to ensure genome stability. Despite extensive efforts, our knowledge of DSB-induced chromatin still remains fragmented. Here, we describe the distribution of 20 chromatin features at multiple DSBs spread throughout the human genome using ChIP-seq. We provide the most comprehensive picture of the chromatin landscape set up at DSBs and identify NHEJ- and HR-specific chromatin events. This study revealed the existence of a DSB-induced monoubiquitination-to-acetylation switch on histone H2B lysine 120, likely mediated by the SAGA complex, as well as higher-order signaling at HR-repaired DSBs whereby histone H1 is evicted while ubiquitin and 53BP1 accumulate over the entire γH2AX domains.