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Nat Struct Mol Biol. 2014 Apr;21(4):366-74. doi: 10.1038/nsmb.2796. Epub 2014 Mar 23.

Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks.

Author information

1
1] Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, Université de Toulouse, Université Paul Sabatier, Toulouse, France. [2] CNRS, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, Toulouse, France.
2
1] Gurdon Institute, University of Cambridge, Cambridge, UK. [2] Department of Biochemistry, University of Cambridge, Cambridge, UK. [3] Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
3
Bioinformatic Plateau I2MC, INSERM, University of Toulouse, Toulouse, France.
4
1] Gurdon Institute, University of Cambridge, Cambridge, UK. [2].

Abstract

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.

PMID:
24658350
PMCID:
PMC4300393
DOI:
10.1038/nsmb.2796
[Indexed for MEDLINE]
Free PMC Article

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