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Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks
Open accessAbstract
Although both homologous recombination (HR) and nonhomologous end joining can repair DNA double-strand breaks (DSBs), the mechanisms by which one of these pathways is chosen over the other remain unclear. Here we show that transcriptionally active chromatin is preferentially repaired by HR. Using chromatin immunoprecipitation-sequencing (ChIP-seq) to analyze repair of multiple DSBs induced throughout the human genome, we identify an HR-prone subset of DSBs that recruit the HR protein RAD51, undergo resection and rely on RAD51 for efficient repair. These DSBs are located in actively transcribed genes and are targeted to HR repair via the transcription elongation-associated mark trimethylated histone H3 K36. Concordantly, depletion of SETD2, the main H3 K36 trimethyltransferase, severely impedes HR at such DSBs. Our study thereby demonstrates a primary role in DSB repair of the chromatin context in which a break occurs.
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“consistent with a role for (epi)genomic context in modulating DSB repair efficiency (44–47).”
From Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability (2016) · cites this paper as [44]
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Metadata
- Authors
- Aymard, F., Bugler, B., Schmidt, C. K., Guillou, E., Caron, P., Briois, S., Iacovoni, J. S., Daburon, V., Miller, K. M., Jackson, S. P., & Legube, G.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Cambridge (GB)
- Inserm (FR)
- Corresponding author
- Legube, Gaëlle
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2014-03-23
- Volume
- 21
- Issue
- 4
- Pages
- 366-374
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC4300393
- OpenAlex
- W2097027640
- Cited by
- 668
- References
- 52
- Citations by year
- 2026: 33 · 2025: 51 · 2024: 50 · 2023: 47 · 2022: 65 · 2021: 79 · 2020: 69 · 2019: 53 · 2018: 47 · 2017: 62 · 2016: 52 · 2015: 40 · 2014: 18
- FWCI
- 23.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (086861, 092096)
- European Molecular Biology Laboratory
- Broad Institute
- Cancer Research UK (C6/A11226, 11224, A11224)
- Agence Nationale de la Recherche (ANR-09-JCJC-0138)
- National Cancer Institute (F31CA260794)
- 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 › CRISPR and Genetic Engineering
- Keywords
- DNA double-strand breaks, homologous recombination, non-homologous end joining, RAD51, SETD2, transcriptionally active chromatin, DNA resection, transcription elongation, chromatin context
- MeSH terms
- Cell Line, Chromatin, DNA Repair, DNA-Binding Proteins, Histones, Humans, Neoplasm Proteins, Transcription, Genetic, Rad51 Recombinase, DNA Breaks, Double-Stranded, Homologous Recombination, DNA End-Joining Repair
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