RSC facilitates Rad59-dependent homologous recombination between sister chromatids by promoting cohesin loading at DNA double-strand breaks

Mol Cell Biol. 2011 Oct;31(19):3924-37. doi: 10.1128/MCB.01269-10. Epub 2011 Aug 1.

Abstract

Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes contribute to homologous DNA repair are unknown. Here we have systematically assessed the role of budding yeast RSC (remodel structure of chromatin), an abundant, ATP-dependent chromatin-remodeling complex, in the cellular response to spontaneous and induced DNA damage. RSC physically interacts with the recombination protein Rad59 and functions in homologous recombination. Multiple recombination assays revealed that RSC is uniquely required for recombination between sister chromatids by virtue of its ability to recruit cohesin at DNA breaks and thereby promoting sister chromatid cohesion. This study provides molecular insights into how chromatin remodeling contributes to DNA repair and maintenance of chromatin fidelity in the face of DNA damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / physiology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatids / metabolism*
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cohesins
  • DNA Breaks, Double-Stranded*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Homologous Recombination*
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Recombinational DNA Repair*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • NPL6 protein, S cerevisiae
  • RAD59 protein, S cerevisiae
  • RSC complex, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Rad51 Recombinase