Mutations that prevent methylation of cohesin render sensitivity to DNA damage in S. pombe

J Cell Sci. 2018 Jul 6;131(13):jcs214924. doi: 10.1242/jcs.214924.

Abstract

The canonical role of cohesin is to mediate sister chromatid cohesion. In addition, cohesin plays important roles in processes such as DNA repair and regulation of gene expression. Mounting evidence suggests that various post-translational modifications, including phosphorylation, acetylation and sumoylation regulate cohesin functions. Our mass spectrometry analysis of cohesin purified from Schizosaccharomyces pombe cells revealed that the cohesin subunit Psm1 is methylated on two evolutionarily conserved lysine residues, K536 and K1200. We found that mutations that prevent methylation of Psm1 K536 and K1200 render sensitivity to DNA-damaging agents and show positive genetic interactions with mutations in genes encoding the Mus81-Eme1 endonuclease. Yeast two-hybrid and co-immunoprecipitation assays showed that there were interactions between subunits of the cohesin and Mus81-Eme1 complexes. We conclude that cohesin is methylated and that mutations that prevent methylation of Psm1 K536 and K1200 show synthetic phenotypes with mutants defective in the homologous recombination DNA repair pathway.

Keywords: Cohesin; DNA repair; Meiosis; Mitosis; Schizosaccharomyces pombe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Endonucleases / genetics*
  • Endonucleases / metabolism
  • Methylation
  • Mutation
  • Protein Binding
  • Schizosaccharomyces / chemistry
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics*
  • Schizosaccharomyces pombe Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MUS81 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • cohesins
  • psm1 protein, S pombe
  • Eme1 protein, S pombe
  • Endonucleases