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

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromatin / genetics*
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics*
  • Genomic Instability / genetics
  • Histones / genetics*
  • Homologous Recombination / genetics
  • Humans
  • K562 Cells
  • Tumor Suppressor p53-Binding Protein 1 / genetics


  • Chromatin
  • Histones
  • Tumor Suppressor p53-Binding Protein 1