A Role for Chromatin Remodeling in Cohesin Loading onto Chromosomes

Mol Cell. 2019 May 16;74(4):664-673.e5. doi: 10.1016/j.molcel.2019.02.027. Epub 2019 Mar 25.

Abstract

Cohesin is a conserved, ring-shaped protein complex that topologically embraces DNA. Its central role in genome organization includes functions in sister chromatid cohesion, DNA repair, and transcriptional regulation. Cohesin loading onto chromosomes requires the Scc2-Scc4 cohesin loader, whose presence on chromatin in budding yeast depends on the RSC chromatin remodeling complex. Here we reveal a dual role of RSC in cohesin loading. RSC acts as a chromatin receptor that recruits Scc2-Scc4 by a direct protein interaction independent of chromatin remodeling. In addition, chromatin remodeling is required to generate a nucleosome-free region that is the substrate for cohesin loading. An engineered cohesin loading module can be created by fusing the Scc2 C terminus to RSC or to other chromatin remodelers, but not to unrelated DNA binding proteins. These observations demonstrate the importance of nucleosome-free DNA for cohesin loading and provide insight into how cohesin accesses DNA during its varied chromosomal activities.

Keywords: RSC; Saccharomyces cerevisiae; Scc2-Scc4; chromatin remodeling; cohesin; cohesin loader; sister chromatid cohesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Chromatin Assembly and Disassembly / genetics*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosome Segregation / genetics
  • Chromosomes / genetics
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics
  • Nucleosomes / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Sister Chromatid Exchange
  • Transcription, Genetic

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nucleosomes
  • SCC2 protein, S cerevisiae
  • SCC4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • cohesins