LBCMCP, Centre de Biologie Integrative (CBI), CNRS, Université de Toulouse, UT3, Toulouse 31062, France.
LBCMCP, Centre de Biologie Integrative (CBI), CNRS, Université de Toulouse, UT3, Toulouse 31062, France.
Mol Cell. 2018 Oct 18;72(2):250-262.e6. doi: 10.1016/j.molcel.2018.08.020. Epub 2018 Sep 27.
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.
双链断裂（DSBs）是非常有害的 DNA 损伤，可导致致癌驱动突变和易位。非同源末端连接（NHEJ）和同源重组（HR）代表在染色质背景下起作用的两种主要修复途径，以确保基因组稳定性。尽管付出了巨大努力，但我们对 DSB 诱导染色质的了解仍然支离破碎。在这里，我们使用 ChIP-seq 描述了分布在整个人类基因组中的多个 DSB 处的 20 种染色质特征的分布。我们提供了 DSB 处染色质景观的最全面描述，并确定了 NHEJ 和 HR 特异性染色质事件。这项研究揭示了 SAGA 复合物介导的组蛋白 H2B 赖氨酸 120 的 DSB 诱导单泛素化-乙酰化开关的存在，以及 HR 修复的 DSB 处的更高阶信号，其中组蛋白 H1 被驱逐，而泛素和 53BP1 则在整个 γH2AX 结构域上积累。
