2. Academic Validation
  3. Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1

Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1

  • Sci Rep. 2014 May 6;4:4863. doi: 10.1038/srep04863.
Shinichi Machida 1,  Motoki Takaku 1,  Masae Ikura 2,  Jiying Sun 3,  Hidekazu Suzuki 3,  Wataru Kobayashi 4,  Aiko Kinomura 3,  Akihisa Osakabe 4,  Hiroaki Tachiwana 4,  Yasunori Horikoshi 3,  Atsuhiko Fukuto 3,  Ryo Matsuda 2,  Kiyoe Ura 5,  Satoshi Tashiro 3,  Tsuyoshi Ikura 2,  Hitoshi Kurumizaka 4
Affiliations

Affiliations

  • 1 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].
  • 2 Department of Mutagenesis, Division of Chromatin Regulatory Network, Radiation Biology Center, Kyoto University, Yoshidakonoe, Sakyo-ku, Kyoto 606-8501, Japan.
  • 3 Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
  • 4 Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
  • 5 Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
PMID: 24798879 DOI: 10.1038/srep04863
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.

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