Ctf4 Links DNA Replication with Sister Chromatid Cohesion Establishment by Recruiting the Chl1 Helicase to the Replisome

Mol Cell. 2016 Aug 4;63(3):371-84. doi: 10.1016/j.molcel.2016.05.036. Epub 2016 Jul 7.

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.

MeSH terms

  • Acetyltransferases / metabolism
  • Acylation
  • Cell Cycle Proteins / metabolism
  • Chromatids / enzymology*
  • Chromatids / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomal Proteins, Non-Histone / ultrastructure
  • Chromosomes, Fungal / enzymology*
  • Chromosomes, Fungal / genetics
  • DNA, Fungal / biosynthesis*
  • DNA, Fungal / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / ultrastructure
  • Microscopy, Electron, Transmission
  • Models, Molecular
  • Multiprotein Complexes
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • S Phase*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / ultrastructure
  • Structure-Activity Relationship
  • Time Factors

Substances

  • CHL1 protein, S cerevisiae
  • CTF4 protein, S cerevisiae
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • Acetyltransferases
  • ECO1 protein, S cerevisiae