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

Shinichi Machida, Motoki Takaku, Masae Ikura, Jiying Sun, Hidekazu Suzuki, Wataru Kobayashi, Aiko Kinomura, Akihisa Osakabe, Hiroaki Tachiwana, Yasunori Horikoshi, Atsuhiko Fukuto, Ryo Matsuda, Kiyoe Ura, Satoshi Tashiro, Tsuyoshi Ikura, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    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.

    Original languageEnglish
    Article number4863
    JournalScientific Reports
    Volume4
    DOIs
    Publication statusPublished - 2014 May 6

    ASJC Scopus subject areas

    • General

    Fingerprint Dive into the research topics of 'Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1'. Together they form a unique fingerprint.

  • Cite this

    Machida, S., Takaku, M., Ikura, M., Sun, J., Suzuki, H., Kobayashi, W., Kinomura, A., Osakabe, A., Tachiwana, H., Horikoshi, Y., Fukuto, A., Matsuda, R., Ura, K., Tashiro, S., Ikura, T., & Kurumizaka, H. (2014). Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. Scientific Reports, 4, [4863]. https://doi.org/10.1038/srep04863