Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion

Nat Commun. 2019 Nov 15;10(1):5178. doi: 10.1038/s41467-019-13210-5.

Abstract

Genome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid recombination (SCR). To decipher the role of chromatin in eukaryotic DSB repair, here we analyze a collection of yeast chromatin-modifying mutants using a previously developed system for the molecular analysis of repair of replication-born DSBs by SCR based on a mini-HO site. We confirm the candidates through FLP-based systems based on a mutated version of the FLP flipase that causes nicks on either the leading or lagging DNA strands. We demonstrate that Rpd3L and Hda1 histone deacetylase (HDAC) complexes contribute to the repair of replication-born DSBs by facilitating cohesin loading, with no effect on other types of homology-dependent repair, thus preventing genome instability. We conclude that histone deacetylation favors general sister chromatid cohesion as a necessary step in SCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatids / genetics
  • Chromatids / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Repair*
  • DNA Replication
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sister Chromatid Exchange

Substances

  • Saccharomyces cerevisiae Proteins
  • HDA1 protein, S cerevisiae
  • RPD3 protein, S cerevisiae
  • Histone Deacetylases