title: Closing the cohesin ring: structure and function of its Smc3-kleisin interface.
abstract: Through their association with a kleisin subunit (Scc1), cohesin's Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two α helices, forming a four-helix bundle with the coiled coil emerging from Smc3's adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin's association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin's dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gligoris
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Scheinost
authors.affiliation: Max-Planck-Institut für Biochemie, 82152, Martinsried, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bürmann
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Petela
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Medical Research Council (MRC) Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: Kok-Lung
authors.initials: KL
authors.lastname: Chan
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Dunn School of Pathology, University of Oxford, Oxford OX1 3RF, UK.
authors.forename: Pelin
authors.initials: P
authors.lastname: Uluocak
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Beckouët
authors.affiliation: Max-Planck-Institut für Biochemie, 82152, Martinsried, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gruber
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk.
authors.forename: Jan
authors.initials: J
authors.lastname: Löwe
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics; D017124:Conserved Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D009154:Mutation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003432:Cross-Linking Reagents; D004247:DNA; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C490529:MCD1 protein, S cerevisiae; C120372:SMC3 protein, S cerevisiae