title: Ctf4 Links DNA Replication with Sister Chromatid Cohesion Establishment by Recruiting the Chl1 Helicase to the Replisome.
abstract: DNA replication during S phase is accompanied by establishment of sister chromatid cohesion to ensure faithful chromosome segregation. The Eco1 acetyltransferase, helped by factors including Ctf4 and Chl1, concomitantly acetylates the chromosomal cohesin complex to stabilize its cohesive links. Here we show that Ctf4 recruits the Chl1 helicase to the replisome via a conserved interaction motif that Chl1 shares with GINS and polymerase α. We visualize recruitment by EM analysis of a reconstituted Chl1-Ctf4-GINS assembly. The Chl1 helicase facilitates replication fork progression under conditions of nucleotide depletion, partly independently of Ctf4 interaction. Conversely, Ctf4 interaction, but not helicase activity, is required for Chl1's role in sister chromatid cohesion. A physical interaction between Chl1 and the cohesin complex during S phase suggests that Chl1 contacts cohesin to facilitate its acetylation. Our results reveal how Ctf4 forms a replisomal interaction hub that coordinates replication fork progression and sister chromatid cohesion establishment.
authors.affiliation: Chromosome Segregation Laboratory, Francis Crick Institute, London WC2A 3LY, UK.
authors.forename: Catarina P
authors.initials: CP
authors.lastname: Samora
authors.affiliation: Institute of Human Genetics (IGH), CNRS, 34396 Montpellier, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Saksouk
authors.affiliation: Macromolecular Machines Laboratory, Francis Crick Institute, South Mimms EN6 3LD, UK.
authors.forename: Panchali
authors.initials: P
authors.lastname: Goswami
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, Francis Crick Institute, London WC2A 3LY, UK.
authors.forename: Ben O
authors.initials: BO
authors.lastname: Wade
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, Francis Crick Institute, London WC2A 3LY, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Singleton
authors.affiliation: Biomolecular Modelling Laboratory, Francis Crick Institute, London WC2A 3LY, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bates
authors.affiliation: Institute of Human Genetics (IGH), CNRS, 34396 Montpellier, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Lengronne
authors.affiliation: Macromolecular Machines Laboratory, Francis Crick Institute, South Mimms EN6 3LD, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Costa
authors.affiliation: Chromosome Segregation Laboratory, Francis Crick Institute, London WC2A 3LY, UK. Electronic address: frank.uhlmann@crick.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000215:Acylation; D018797:Cell Cycle Proteins / Q000378:metabolism; D002842:Chromatids / Q000201:enzymology* / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015825:Chromosomes, Fungal / Q000201:enzymology* / Q000235:genetics; D004271:DNA, Fungal / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D013997:Time Factors; D000097722:Cohesins
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C066751:CHL1 protein, S cerevisiae; C078338:CTF4 protein, S cerevisiae; C118076:ECO1 protein, S cerevisiae