title: ATM-dependent chromatin remodeler Rsf-1 facilitates DNA damage checkpoints and homologous recombination repair.
abstract: As a member of imitation switch (ISWI) family in ATP-dependent chromatin remodeling factors, RSF complex consists of SNF2h ATPase and Rsf-1. Although it has been reported that SNF2h ATPase is recruited to DNA damage sites (DSBs) in a poly(ADP-ribosyl) polymerase 1 (PARP1)-dependent manner in DNA damage response (DDR), the function of Rsf-1 is still elusive. Here we show that Rsf-1 is recruited to DSBs confirmed by various cellular analyses. Moreover, the initial recruitment of Rsf-1 and SNF2h to DSBs shows faster kinetics than that of γH2AX after micro-irradiation. Signals of Rsf-1 and SNF2h are retained over 30 min after micro-irradiation, whereas γH2AX signals are gradually reduced at 10 min. In addition, Rsf-1 is accumulated at DSBs in ATM-dependent manner, and the putative pSQ motifs of Rsf-1 by ATM are required for its accumulation at DSBs. Furtheremore, depletion of Rsf-1 attenuates the activation of DNA damage checkpoint signals and cell survival upon DNA damage. Finally, we demonstrate that Rsf-1 promotes homologous recombination repair (HRR) by recruiting resection factors RPA32 and Rad51. Thus, these findings reveal a new function of chromatin remodeler Rsf-1 as a guard in DNA damage checkpoints and homologous recombination repair.
authors.affiliation: Department of Biochemistry; Ajou University School of Medicine; Suwon, South Korea; Genomic Instability Research Center; Ajou University School of Medicine; Suwon, South Korea.
authors.forename: Sunwoo
authors.initials: S
authors.lastname: Min
authors.affiliation: Department of Biochemistry; Ajou University School of Medicine; Suwon, South Korea; Genomic Instability Research Center; Ajou University School of Medicine; Suwon, South Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Jo
authors.affiliation: Department of Biochemistry; Ajou University School of Medicine; Suwon, South Korea; Genomic Instability Research Center; Ajou University School of Medicine; Suwon, South Korea.
authors.forename: Ho-Soo
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry; Ajou University School of Medicine; Suwon, South Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Chae
authors.affiliation: Department of Life Science; College of Natural Sciences; Ajou University; Suwon, South Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Genomic Instability Research Center; Ajou University School of Medicine; Suwon, South Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Ji
authors.affiliation: Department of Biochemistry; Ajou University School of Medicine; Suwon, South Korea; Genomic Instability Research Center; Ajou University School of Medicine; Suwon, South Korea.
authors.forename: Hyeseong
authors.initials: H
authors.lastname: Cho
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D059767:Recombinational DNA Repair; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C468783:H2AX protein, human; D006657:Histones; D009687:Nuclear Proteins; C452851:RSF1 protein, human; D015534:Trans-Activators; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human
keywords: ATM; DNA damage checkpoints; DNA double-strand breaks; ISWI chromatin remodeler; Rsf-1; homologous recombination repair