title: Post-replicative repair involves separase-dependent removal of the kleisin subunit of cohesin.
abstract: DNA double-strand break repair is critical for cell viability and involves highly coordinated pathways to restore DNA integrity at the lesion. An early event during homology-dependent repair is resection of the break to generate progressively longer 3' single-strand tails that are used to identify suitable templates for repair. Sister chromatids provide near-perfect sequence homology and are therefore the preferred templates during homologous recombination. To provide a bias for the use of sisters as donors, cohesin--the complex that tethers sister chromatids together--is recruited to the break to enforce physical proximity. Here we show that DNA breaks promote dissociation of cohesin loaded during the previous S phase in budding yeast, and that damage-induced dissociation of cohesin requires separase, the protease that dissolves cohesion in anaphase. Moreover, a separase-resistant allele of the gene coding for the α-kleisin subunit of cohesin, Mcd1 (also known as Scc1), reduces double-strand break resection and compromises the efficiency of repair even when loaded during DNA damage. We conclude that post-replicative DNA repair involves cohesin dissociation by separase to promote accessibility to repair factors during the coordinated cellular response to restore DNA integrity.
authors.affiliation: Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 0NN, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: McAleenan
authors.forename: Andres
authors.initials: A
authors.lastname: Clemente-Blanco
authors.forename: Violeta
authors.initials: V
authors.lastname: Cordon-Preciado
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sen
authors.forename: Miguel
authors.initials: M
authors.lastname: Esteras
authors.forename: Adam
authors.initials: A
authors.lastname: Jarmuz
authors.forename: Luis
authors.initials: L
authors.lastname: Aragón
mesh_terms: D000483:Alleles; D000705:Anaphase; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004261:DNA Replication; D010450:Endopeptidases / Q000378:metabolism*; D016195:G2 Phase; D008677:Metaphase; D011485:Protein Binding; D055550:Protein Stability; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D064247:Separase; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D010450:Endopeptidases; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D064247:Separase; D000097722:Cohesins; C490529:MCD1 protein, S cerevisiae; C577986:ESP1 protein, S cerevisiae