MRX Increases Chromatin Accessibility at Stalled Replication Forks to Promote Nascent DNA Resection and Cohesin Loading

Mol Cell. 2020 Jan 16;77(2):395-410.e3. doi: 10.1016/j.molcel.2019.10.029. Epub 2019 Nov 20.


The recovery of stalled replication forks depends on the controlled resection of nascent DNA and on the loading of cohesin. These processes operate in the context of nascent chromatin, but the impact of nucleosome structure on a fork restart remains poorly understood. Here, we show that the Mre11-Rad50-Xrs2 (MRX) complex acts together with the chromatin modifiers Gcn5 and Set1 and the histone remodelers RSC, Chd1, and Isw1 to promote chromatin remodeling at stalled forks. Increased chromatin accessibility facilitates the resection of nascent DNA by the Exo1 nuclease and the Sgs1 and Chl1 DNA helicases. Importantly, increased ssDNA promotes the recruitment of cohesin to arrested forks in a Scc2-Scc4-dependent manner. Altogether, these results indicate that MRX cooperates with chromatin modifiers to orchestrate the action of remodelers, nucleases, and DNA helicases, promoting the resection of nascent DNA and the loading of cohesin, two key processes involved in the recovery of arrested forks.

Keywords: Gcn5; Mre11; Set1; chromatin modification; cohesin; replication stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA Helicases / genetics
  • DNA Replication / genetics*
  • DNA, Fungal / genetics*
  • DNA-Binding Proteins / genetics*
  • Endodeoxyribonucleases / genetics*
  • Exodeoxyribonucleases / genetics*
  • Nucleosomes / genetics
  • RecQ Helicases / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*


  • CHL1 protein, S cerevisiae
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • DNA-Binding Proteins
  • Nucleosomes
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • XRS2 protein, S cerevisiae
  • cohesins
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae
  • SGS1 protein, S cerevisiae
  • DNA Helicases
  • RecQ Helicases