Histone H2A.Z controls a critical chromatin remodeling step required for DNA double-strand break repair

Mol Cell. 2012 Dec 14;48(5):723-33. doi: 10.1016/j.molcel.2012.09.026. Epub 2012 Oct 30.


Chromatin remodeling during DNA double-strand break (DSB) repair is required to facilitate access to and repair of DSBs. This remodeling requires increased acetylation of histones and a shift in nucleosome organization to create open, relaxed chromatin domains. However, the underlying mechanism driving changes in nucleosome structure at DSBs is poorly defined. Here, we demonstrate that histone H2A.Z is exchanged onto nucleosomes at DSBs by the p400 remodeling ATPase. H2A.Z exchange at DSBs shifts the chromatin to an open conformation and is required for acetylation and ubiquitination of histones and for loading of the brca1 complex. H2A.Z exchange also restricts single-stranded DNA production by nucleases and is required for loading of the Ku70/Ku80 DSB repair protein. H2A.Z exchange therefore promotes specific patterns of histone modification and reorganization of the chromatin architecture, leading to the assembly of a chromatin template that is an efficient substrate for the DSB repair machinery.

Publication types

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

MeSH terms

  • Acetylation
  • Adenosine Triphosphatases / metabolism
  • Antigens, Nuclear / metabolism
  • Binding Sites
  • Binding, Competitive
  • Carrier Proteins / metabolism
  • Chromatin Assembly and Disassembly*
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Dose-Response Relationship, Radiation
  • Endodeoxyribonucleases
  • HEK293 Cells
  • HeLa Cells
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Ku Autoantigen
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation
  • Nucleosomes / chemistry
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Nucleosomes / radiation effects
  • RNA Interference
  • Time Factors
  • Transfection
  • Ubiquitination


  • Antigens, Nuclear
  • Carrier Proteins
  • DNA-Binding Proteins
  • Histones
  • Nuclear Proteins
  • Nucleosomes
  • histone H2A.F-Z
  • Endodeoxyribonucleases
  • RBBP8 protein, human
  • Adenosine Triphosphatases
  • SRCAP protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen