title: Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks.
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.
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Aymard
authors.affiliation: 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.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Bugler
authors.affiliation: 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.
authors.forename: Christine K
authors.initials: CK
authors.lastname: Schmidt
authors.affiliation: 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.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Guillou
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Caron
authors.affiliation: 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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briois
authors.affiliation: Bioinformatic Plateau I2MC, INSERM, University of Toulouse, Toulouse, France.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.affiliation: 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.
authors.forename: Virginie
authors.initials: V
authors.lastname: Daburon
authors.affiliation: 1] Gurdon Institute, University of Cambridge, Cambridge, UK. [2].
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
authors.affiliation: 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.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Legube
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009363:Neoplasm Proteins; C101467:XRCC4 protein, human; C095024:leiomyoma-derived growth factor; D051135:Rad51 Recombinase