title: Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1.
abstract: Homologous recombination plays essential roles in mitotic DNA double strand break (DSB) repair and meiotic genetic recombination. In eukaryotes, RAD51 promotes the central homologous-pairing step during homologous recombination, but is not sufficient to overcome the reaction barrier imposed by nucleosomes. RAD54, a member of the ATP-dependent nucleosome remodeling factor family, is required to promote the RAD51-mediated homologous pairing in nucleosomal DNA. In higher eukaryotes, most nucleosomes form higher-ordered chromatin containing the linker histone H1. However, the mechanism by which RAD51/RAD54-mediated homologous pairing occurs in higher-ordered chromatin has not been elucidated. In this study, we found that a histone chaperone, Nap1, accumulates on DSB sites in human cells, and DSB repair is substantially decreased in Nap1-knockdown cells. We determined that Nap1 binds to RAD54, enhances the RAD54-mediated nucleosome remodeling by evicting histone H1, and eventually stimulates the RAD51-mediated homologous pairing in higher-ordered chromatin containing histone H1.
authors.affiliation: 1] Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan [2].
authors.forename: Shinichi
authors.initials: S
authors.lastname: Machida
authors.affiliation: 1] Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan [2].
authors.forename: Motoki
authors.initials: M
authors.lastname: Takaku
authors.affiliation: Department of Mutagenesis, Division of Chromatin Regulatory Network, Radiation Biology Center, Kyoto University, Yoshidakonoe, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Ikura
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Jiying
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kobayashi
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kinomura
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Osakabe
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tachiwana
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Horikoshi
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Fukuto
authors.affiliation: Department of Mutagenesis, Division of Chromatin Regulatory Network, Radiation Biology Center, Kyoto University, Yoshidakonoe, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsuda
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kiyoe
authors.initials: K
authors.lastname: Ura
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tashiro
authors.affiliation: Department of Mutagenesis, Division of Chromatin Regulatory Network, Radiation Biology Center, Kyoto University, Yoshidakonoe, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*; D012359:tRNA Methyltransferases
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D011506:Proteins; C498548:TRMO protein, human; D012359:tRNA Methyltransferases; D051135:Rad51 Recombinase; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C103532:RAD54L protein, human; D045643:DNA Repair Enzymes