title: FACT Assists Base Excision Repair by Boosting the Remodeling Activity of RSC.
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.
authors.affiliation: Université Joseph Fourier-Grenoble 1, INSERM Institut Albert Bonniot U823, Site Santé, Grenoble, France.|Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, LBMC CNRS/ENSL/UCBL UMR5239 & Institut NeuroMyoGène-INMG CNRS/UCBL UMR5310, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: John Lalith
authors.initials: JL
authors.lastname: Charles Richard
authors.affiliation: Université Joseph Fourier-Grenoble 1, INSERM Institut Albert Bonniot U823, Site Santé, Grenoble, France.|Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, LBMC CNRS/ENSL/UCBL UMR5239 & Institut NeuroMyoGène-INMG CNRS/UCBL UMR5310, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Manu Shubhdarshan
authors.initials: MS
authors.lastname: Shukla
authors.affiliation: Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, LBMC CNRS/ENSL/UCBL UMR5239 & Institut NeuroMyoGène-INMG CNRS/UCBL UMR5310, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Menoni
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Parc d'Innovation, Illkirch, France.
authors.forename: Khalid
authors.initials: K
authors.lastname: Ouararhni
authors.affiliation: Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, LBMC CNRS/ENSL/UCBL UMR5239 & Institut NeuroMyoGène-INMG CNRS/UCBL UMR5310, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Imtiaz Nisar
authors.identifier: 0000-0002-1137-2569
authors.initials: IN
authors.lastname: Lone
authors.affiliation: Université Joseph Fourier-Grenoble 1, INSERM Institut Albert Bonniot U823, Site Santé, Grenoble, France.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Roulland
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Parc d'Innovation, Illkirch, France.
authors.forename: Christophe
authors.identifier: 0000-0001-8124-5883
authors.initials: C
authors.lastname: Papin
authors.affiliation: Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, LBMC CNRS/ENSL/UCBL UMR5239 & Institut NeuroMyoGène-INMG CNRS/UCBL UMR5310, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Ben Simon
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Tapas
authors.initials: T
authors.lastname: Kundu
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Parc d'Innovation, Illkirch, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Hamiche
authors.affiliation: Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, LBMC CNRS/ENSL/UCBL UMR5239 & Institut NeuroMyoGène-INMG CNRS/UCBL UMR5310, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Angelov
authors.affiliation: Université Joseph Fourier-Grenoble 1, INSERM Institut Albert Bonniot U823, Site Santé, Grenoble, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dimitrov
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics*; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000096:biosynthesis / Q000235:genetics*; D014498:Uracil / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D006657:Histones; D009707:Nucleosomes; C103337:RSC complex, S cerevisiae; C073537:SSRP1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D014498:Uracil