title: The ACF1 complex is required for DNA double-strand break repair in human cells.
abstract: DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ) or homologous recombination (HR), but cellular repair processes remain elusive. We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H, accumulate rapidly at DSBs and are required for DSB repair in human cells. If the expression of ACF1 or SNF2H is suppressed, cells become extremely sensitive to X-rays and chemical treatments producing DSBs, and DSBs remain unrepaired. ACF1 interacts directly with KU70 and is required for the accumulation of KU proteins at DSBs. The KU70/80 complex becomes physically more associated with the chromatin-remodeling factors of the CHRAC complex, which includes ACF1, SNF2H, CHRAC15, and CHRAC17, after treatments producing DSBs. Furthermore, the frequency of NHEJ as well as HR induced by DSBs in chromosomal DNA is significantly decreased in cells depleted of either of these factors. Thus, ACF1 and its complexes play important roles in DSBs repair.
authors.affiliation: Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryomachi 4-1, Sendai 980-8575, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.forename: Ayako
authors.initials: A
authors.lastname: Ui
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakajima
authors.forename: Kotomi
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Mikiko
authors.initials: M
authors.lastname: Hoshi
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.forename: Susan M
authors.initials: SM
authors.lastname: Janicki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ogiwara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kanno
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D034961:Antigens, Nuclear / Q000378:metabolism; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004258:DNA Polymerase III / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D000072200:Ku Autoantigen; D009698:Nucleoproteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014466:Ultraviolet Rays; D000092468:Bromodomain Containing Proteins
chemical_list: D000251:Adenosine Triphosphatases; D034961:Antigens, Nuclear; D002868:Chromosomal Proteins, Non-Histone; D004258:DNA Polymerase III; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D000072200:Ku Autoantigen; D009698:Nucleoproteins; D014157:Transcription Factors; C492319:BAZ1A protein, human; D000092468:Bromodomain Containing Proteins; C413904:CHRAC1 protein, human; C413905:POLE3 protein, human; C409462:SMARCA5 protein, human; C000606509:Xrcc6 protein, human