title: DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain.
abstract: The postreplicative repair of double-strand breaks (DSBs) is thought to require sister chromatid cohesion, provided by the cohesin complex along the chromosome arms. A further specialized role for cohesin in DSB repair is suggested by its de novo recruitment to regions of DNA damage in mammals. Here, we show in budding yeast that a single DSB induces the formation of a approximately 100 kb cohesin domain around the lesion. Our analyses suggest that the primary DNA damage checkpoint kinases Mec1p and Tel1p phosphorylate histone H2AX to generate a large domain, which is permissive for cohesin binding. Cohesin binding to the phospho-H2AX domain is enabled by Mre11p, a component of a critical repair complex, and Scc2p, a component of the cohesin loading machinery that is necessary for sister chromatid cohesion. We also provide evidence that the DSB-induced cohesin domain functions in postreplicative repair.
authors.affiliation: Howard Hughes Medical Institute, Department of Embryology, The Carnegie Institution of Washington, Baltimore, MD 21210, USA.
authors.forename: Elçin
authors.initials: E
authors.lastname: Unal
authors.forename: Ayelet
authors.initials: A
authors.lastname: Arbel-Eden
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sattler
authors.forename: Robert
authors.initials: R
authors.lastname: Shroff
authors.forename: Michael
authors.initials: M
authors.lastname: Lichten
authors.forename: James E
authors.initials: JE
authors.lastname: Haber
authors.forename: Douglas
authors.initials: D
authors.lastname: Koshland
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000378:metabolism; D005656:Fungal Proteins; D005785:Gene Conversion / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins; D006657:Histones; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C410592:SCC2 protein, S cerevisiae; C410593:SCC4 protein, S cerevisiae; C475961:gamma-H2AX protein, mouse; C067022:RAD53 protein, S cerevisiae; C094191:MRE11 protein, S cerevisiae