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

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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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. Using ChIP-seq in a cell line where multiple annotated DNA double-strand breaks can be induced on the human genome, Clouaire et al. report a comprehensive view of the chromatin landscape set up at DSBs and decipher the chromatin signature associated with HR and NHEJ repair.

Original languageEnglish (US)
Pages (from-to)250-262.e6
JournalMolecular Cell
Volume72
Issue number2
DOIs
StatePublished - Oct 18 2018

Keywords

  • 53BP1
  • ChIP-seq
  • DNA double-strand breaks
  • DSB repair
  • chromatin
  • histone H1
  • histone modifications
  • homologous recombination
  • non-homologous end joining
  • γH2AX

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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