Histone H2A.Z Controls a Critical Chromatin Remodeling Step Required for DNA Double-Strand Break Repair
Open accessAbstract
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.
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- Authors
- Xu, Y., Ayrapetov, M. K., Xu, C., Gursoy-Yuzugullu, O., Hu, Y., & Price, B. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Price, Brendan D.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 48
- Issue
- 5
- Pages
- 723-733
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3525728
- OpenAlex
- W2118997256
- Cited by
- 336
- References
- 57
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 29 · 2023: 14 · 2022: 30 · 2021: 25 · 2020: 33 · 2019: 23 · 2018: 23 · 2017: 30 · 2016: 17 · 2015: 29 · 2014: 33 · 2013: 27 · 2012: 1
- FWCI
- 11.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- National Cancer Institute (R01CA064585, R01CA093602, CA64585, CA93602)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- histone H2A.Z, DNA double-strand break repair, chromatin remodeling, histone acetylation, histone ubiquitination, nucleosome structure, Ku70/Ku80, single-stranded DNA, histone modifications
- MeSH terms
- Ku Autoantigen, Acetylation, Adenosine Triphosphatases, Binding Sites, Binding, Competitive, Carrier Proteins, DNA Repair, DNA-Binding Proteins, Dose-Response Relationship, Radiation, Endodeoxyribonucleases, HeLa Cells, Histones, Humans, Nuclear Proteins, Nucleic Acid Conformation, Nucleosomes, Time Factors, Transfection, RNA Interference, Antigens, Nuclear, Chromatin Assembly and Disassembly, DNA Breaks, Double-Stranded, Ubiquitination, HEK293 Cells, DNA End-Joining Repair
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