Distinct targets of the Eco1 acetyltransferase modulate cohesion in S phase and in response to DNA damage

Mol Cell. 2009 May 15;34(3):311-21. doi: 10.1016/j.molcel.2009.04.008.

Abstract

Chromosome segregation and the repair of DNA double-strand breaks (DSBs) require cohesin, the protein complex that mediates sister chromatid cohesion. Cohesion requires both a chromatin binding step and a subsequent tethering step called cohesion generation. Here we provide insight into how cohesion generation is restricted to S phase but can be activated in G2/M by a DSB in budding yeast. We show that Wpl1p inhibits cohesion in G2/M. A DSB counteracts Wpl1p and stimulates cohesion generation by first inducing the phosphorylation of the Mcd1p subunit of cohesin. This phosphorylation activates Eco1p-dependent acetylation of Mcd1p, which in turn antagonizes Wpl1p. Previous studies show that Eco1p antagonizes Wpl1p in S phase by acetylating the Smc3p subunit of cohesin. We show that Mcd1p and Smc3p acetylation antagonize Wpl1p only in their proper context. Thus, Eco1p antagonizes Wpl1p in distinct ways to modulate cohesion generation during the cell cycle and after DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology
  • Checkpoint Kinase 1
  • Chondroitin Sulfate Proteoglycans / chemistry
  • Chondroitin Sulfate Proteoglycans / genetics
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Chromatids / metabolism*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Breaks, Double-Stranded*
  • G2 Phase / physiology
  • Lysine / metabolism
  • Models, Molecular
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • S Phase / physiology*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Chondroitin Sulfate Proteoglycans
  • Chromosomal Proteins, Non-Histone
  • MCD1 protein, S cerevisiae
  • Nuclear Proteins
  • RAD61 protein, S cerevisiae
  • Recombinant Fusion Proteins
  • SMC3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • Acetyltransferases
  • ECO1 protein, S cerevisiae
  • Protein Kinases
  • Checkpoint Kinase 1
  • Lysine