FACT Assists Base Excision Repair by Boosting the Remodeling Activity of RSC

PLoS Genet. 2016 Jul 28;12(7):e1006221. doi: 10.1371/journal.pgen.1006221. eCollection 2016 Jul.

Abstract

FACT, in addition to its role in transcription, is likely implicated in both transcription-coupled nucleotide excision repair and DNA double strand break repair. Here, we present evidence that FACT could be directly involved in Base Excision Repair and elucidate the chromatin remodeling mechanisms of FACT during BER. We found that, upon oxidative stress, FACT is released from transcription related protein complexes to get associated with repair proteins and chromatin remodelers from the SWI/SNF family. We also showed the rapid recruitment of FACT to the site of damage, coincident with the glycosylase OGG1, upon the local generation of oxidized DNA. Interestingly, FACT facilitates uracil-DNA glycosylase in the removal of uracil from nucleosomal DNA thanks to an enhancement in the remodeling activity of RSC. This discloses a novel property of FACT wherein it has a co-remodeling activity and strongly enhances the remodeling capacity of the chromatin remodelers. Altogether, our data suggest that FACT may acts in concert with RSC to facilitate excision of DNA lesions during the initial step of BER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin Assembly and Disassembly / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • DNA Damage / genetics
  • DNA Repair / genetics*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • HeLa Cells
  • High Mobility Group Proteins / biosynthesis
  • High Mobility Group Proteins / genetics*
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Nucleosomes / genetics
  • Oxidative Stress / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Transcription Factors / genetics
  • Transcription, Genetic*
  • Transcriptional Elongation Factors / biosynthesis
  • Transcriptional Elongation Factors / genetics*
  • Uracil / metabolism
  • Xenopus laevis

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Histones
  • Nucleosomes
  • RSC complex, S cerevisiae
  • SSRP1 protein, human
  • SWI-SNF-B chromatin-remodeling complex
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Transcriptional Elongation Factors
  • Uracil

Grant support

The research leading to these results has received funding from: the Université de Strasbourg https://www.unistra.fr/index.php?id=accueil to AH, the Université Grenoble Alpes http://www.univ-grenoble-alpes.fr/ to SD, the Université de Lyon http://www.universite-lyon.fr/ to DA, the Centre National de la Recherche Scientifique–CNRS http://www.cnrs.fr/ to DA, SD and AH, the Institut National de la Santé et de la Recherche Médicale-INSERM (Plan Cancer) http://www.inserm.fr/ to SD and by grants from: the European Union's Seventh Framework Programme FP7/2007-2013/ http://ec.europa.eu/research/index.cfm Marie Curie Actions grant agreement n°289611 to SD and DA and COST Action CM1201 “Biomimetic Radical Chemistry” to DA, the Association pour la Recherche sur le Cancer-ARC http://www.fondation-arc.org/ Grant n° SFI20101201424 to DA, the Institut National du Cancer—INCa http://www.e-cancer.fr/ grant agreement numbers INCa_4496, INCa_4454 and INCa_PLBIO15-245 to AH and SD, the Agence Nationale de la Recherche-ANR http://www.agence-nationale-recherche.fr/ grant agreement numbers: ANR-12-BSV8-0018 to AH and SD, ANR-14-CE09-0019 to AH and SD and ANR-12-BSV5-0017 to DA and SD, the Fondation pour la Recherche Médicale-FRM https://www.frm.org/ grant n°DEP20131128521 to SD, the Université de Strasbourg Institut d’Etudes Avancées http://www.usias.fr/ grant USIAS-2015-42 to AH, the Ligue Nationale contre le Cancer https://www.ligue-cancer.net/ Équipe labellisée to AH and SD, and post-doc support to HM. Funding for open access charge: the Agence Nationale de la Recherche-ANR http://www.agence-nationale-recherche.fr/ grant agreement n° ANR- 12-BSV5-0017. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.