title: Structural evidence for Scc4-dependent localization of cohesin loading.
abstract: The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2(NIPBL)/Scc4(Mau2) (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesin loading is essential for cell division, and partial defects cause chromosome missegregation and aberrant transcriptional regulation, leading to severe developmental defects in multicellular organisms. We present here a crystal structure showing the interaction between Scc2 and Scc4. Scc4 is a TPR array that envelops an extended Scc2 peptide. Using budding yeast, we demonstrate that a conserved patch on the surface of Scc4 is required to recruit Scc2/4 to centromeres and to build pericentromeric cohesion. These findings reveal the role of Scc4 in determining the localization of cohesin loading and establish a molecular basis for Scc2/4 recruitment to centromeres.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hinshaw
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Vasso
authors.initials: V
authors.lastname: Makrantoni
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alastair
authors.identifier: http://orcid.org/0000-0001-9207-6050
authors.initials: A
authors.lastname: Kerr
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Adèle L
authors.initials: AL
authors.lastname: Marston
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004271:DNA, Fungal / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C410592:SCC2 protein, S cerevisiae; C410593:SCC4 protein, S cerevisiae
keywords: S. cerevisiae; biophysics; cell biology; centromere; cohesin loading; sister chromatid cohesion; structural biology