title: Cohesin association to replication sites depends on rad50 and promotes fork restart.
abstract: The cohesin complex holds together newly replicated chromatids and is involved in diverse pathways that preserve genome integrity. We show that in budding yeast, cohesin is transiently recruited to active replication origins, and it spreads along DNA as forks progress. When DNA synthesis is impeded, cohesin accumulates at replication sites and is critical for the recovery of stalled forks. Cohesin enrichment at replication forks does not depend on γH2A(X) formation, which differs from its loading requirements at DNA double-strand breaks (DSBs). However, cohesin localization is largely reduced in rad50Δ mutants and in cells lacking both Mec1 and Tel1 checkpoint kinases. Interestingly, cohesin loading at replication sites depends on the structural features of Rad50 that are important for bridging sister chromatids, including the CXXC hook domain and the length of the coiled-coil extensions. Together, these data reveal a function for cohesin in the maintenance of genome integrity during S phase.
authors.affiliation: Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB Canada T2N 4N1.|Institute of Human Genetics, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Tittel-Elmer
authors.affiliation: Institute of Human Genetics, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Lengronne
authors.affiliation: Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB Canada T2N 4N1.
authors.forename: Marta B
authors.initials: MB
authors.lastname: Davidson
authors.affiliation: Institute of Human Genetics, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bacal
authors.affiliation: Institute of Human Genetics, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: François
authors.affiliation: Laboratory of Chromosome Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hohl
authors.affiliation: Laboratory of Chromosome Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: John H J
authors.initials: JHJ
authors.lastname: Petrini
authors.affiliation: Institute of Human Genetics, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasero
authors.affiliation: Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB Canada T2N 4N1.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cobb
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006657:Histones / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D006918:Hydroxyurea; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C086930:RAD50 protein, S cerevisiae; C507778:gammaH2AX protein, S cerevisiae; C088937:MEC1 protein, S cerevisiae