title: Cohesin protects genes against γH2AX Induced by DNA double-strand breaks.
abstract: Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome.
authors.affiliation: Université de Toulouse, UPS, LBCMCP, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Caron
authors.forename: Francois
authors.initials: F
authors.lastname: Aymard
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briois
authors.forename: Yvan
authors.initials: Y
authors.lastname: Canitrot
authors.forename: Beatrix
authors.initials: B
authors.lastname: Bugler
authors.forename: Laurent
authors.initials: L
authors.lastname: Massip
authors.forename: Ana
authors.initials: A
authors.lastname: Losada
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Legube
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D024363:Transcription Initiation Site; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D010750:Phosphoproteins; D013629:Tamoxifen; D000097722:Cohesins; C468783:H2AX protein, human; C429022:RAD21 protein, human; C492318:SMC3 protein, human; C016601:afimoxifene