title: Releasing Activity Disengages Cohesin's Smc3/Scc1 Interface in a Process Blocked by Acetylation.
abstract: Sister chromatid cohesion conferred by entrapment of sister DNAs within a tripartite ring formed between cohesin's Scc1, Smc1, and Smc3 subunits is created during S and destroyed at anaphase through Scc1 cleavage by separase. Cohesin's association with chromosomes is controlled by opposing activities: loading by Scc2/4 complex and release by a separase-independent releasing activity as well as by cleavage. Coentrapment of sister DNAs at replication is accompanied by acetylation of Smc3 by Eco1, which blocks releasing activity and ensures that sisters remain connected. Because fusion of Smc3 to Scc1 prevents release and bypasses the requirement for Eco1, we suggested that release is mediated by disengagement of the Smc3/Scc1 interface. We show that mutations capable of bypassing Eco1 in Smc1, Smc3, Scc1, Wapl, Pds5, and Scc3 subunits reduce dissociation of N-terminal cleavage fragments of Scc1 (NScc1) from Smc3. This process involves interaction between Smc ATPase heads and is inhibited by Smc3 acetylation.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Laboratoire de Biologie Moléculaire Eucaryote, UMR 5099 University Paul Sabatier Toulouse III CNRS, 118, Route de Narbonne, 31062 Toulouse, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Beckouët
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Madhusudhan
authors.initials: M
authors.lastname: Srinivasan
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Maurici Brunet
authors.initials: MB
authors.lastname: Roig
authors.affiliation: Genome Centre, University of Sussex, Sussex House, Brighton BN1 9RH, UK.
authors.forename: Kok-Lung
authors.initials: KL
authors.lastname: Chan
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Scheinost
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Batty
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Petela
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gligoris
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Smith
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Lana
authors.initials: L
authors.lastname: Strmecki
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Rowland
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: kim.nasmyth@bioch.ox.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C490529:MCD1 protein, S cerevisiae; C120372:SMC3 protein, S cerevisiae