Histone H2A.Z Controls a Critical Chromatin Remodeling Step Required for DNA Double-Strand Break Repair

Ye Xu, Marina K. Ayrapetov, Chang Xu, Ozge Gursoy-Yuzugullu, Yiduo Hu, Brendan D. Price

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)723-733
Number of pages11
JournalMolecular Cell
Volume48
Issue number5
DOIs
StatePublished - Dec 14 2012

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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