title: Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction.
abstract: Although mammalian SWI/SNF chromatin remodeling complexes have been well established to play important role in transcription, their role in DNA repair has remained largely unexplored. Here we show that inactivation of the SWI/SNF complexes and downregulation of the catalytic core subunits of the complexes both result in inefficient DNA double-strand break (DSB) repair and increased DNA damage sensitivity as well as a large defect in H2AX phosphorylation (gamma-H2AX) and nuclear focus formation after DNA damage. The expression of most DSB repair genes remains unaffected and DNA damage checkpoints are grossly intact in the cells inactivated for the SWI/SNF complexes. Although the SWI/SNF complexes do not affect the expression of ATM, DNA-PK and ATR, or their activation and/or recruitment to DSBs, they rapidly bind to DSB-surrounding chromatin via interaction with gamma-H2AX in the manner that is dependent on the amount of DNA damage. Given the crucial role for gamma-H2AX in efficient DSB repair, these results suggest that the SWI/SNF complexes facilitate DSB repair, at least in part, by promoting H2AX phosphorylation by directly acting on chromatin.
authors.affiliation: Division of Molecular Life Sciences, Department of Life Science and Center for Cell Signaling Research, Ewha Woman's University, Seoul, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Park
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Han-Sae
authors.initials: HS
authors.lastname: Lee
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Shin-Kyoung
authors.initials: SK
authors.lastname: Hur
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Imbalzano
authors.forename: Jongbum
authors.initials: J
authors.lastname: Kwon
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006657:Histones / Q000096:biosynthesis*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D009687:Nuclear Proteins; D021122:Protein Subunits; C084011:SMARCA2 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D045643:DNA Repair Enzymes