title: Pds5 promotes and protects cohesin acetylation.
abstract: Cohesin's Smc1 and Smc3 subunits form V-shaped heterodimers, the nucleotide binding domains (NBDs) of which bind the C- and N-terminal domains, respectively, of the α-kleisin subunit, forming a large tripartite ring within in which sister DNAs are entrapped, and thereby held together (sister chromatid cohesion). During replication, establishment of stable cohesion is dependent on Eco1-mediated acetylation of Smc3's NBD, which is thought to prevent dissociation of α-kleisin from Smc3, thereby locking shut a "DNA exit gate." How Scc3 and Pds5, regulatory subunits bound to α-kleisin, regulate cohesion establishment and maintenance is poorly understood. We show here that by binding to α-kleisin adjacent to its Smc3 nucleotide binding N-terminal domain, Pds5 not only promotes cohesin's release from chromatin but also mediates de novo acetylation of Smc3 by Eco1 during S phase and subsequently prevents de-acetylation by the deacetylase Hos1/HDAC8. By first promoting cohesin's release from chromosomes and subsequently creating and guarding the chemical modification responsible for blocking release, Pds5 enables chromosomal cohesin to switch during S phase from a state of high turnover to one capable of tenaciously holding sister chromatids together for extended periods of time, a duality that has hitherto complicated analysis of this versatile cohesin subunit.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
authors.forename: Kok-Lung
authors.initials: KL
authors.lastname: Chan
authors.forename: Thomas
authors.initials: T
authors.lastname: Gligoris
authors.forename: William
authors.initials: W
authors.lastname: Upcher
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kato
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
authors.forename: Frédéric
authors.initials: F
authors.lastname: Beckouët
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D000097722:Cohesins
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D006655:Histone Deacetylases; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C427726:PDS5 protein, S cerevisiae; C120372:SMC3 protein, S cerevisiae; C118076:ECO1 protein, S cerevisiae
keywords: cell; gene