The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast

Nucleic Acids Res. 2017 Jun 20;45(11):6404-6416. doi: 10.1093/nar/gkx240.

Abstract

Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin.

MeSH terms

  • Adenosine Triphosphatases / physiology*
  • Cell Cycle Proteins / metabolism*
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Fungal / metabolism
  • Cohesins
  • DNA, Ribosomal / genetics
  • Protein Stability
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sister Chromatid Exchange

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA, Ribosomal
  • MCD1 protein, S cerevisiae
  • SCC2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphatases
  • Irc5 protein, S cerevisiae