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- Title
Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1.
- Authors
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
- 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.
- Subjects
CHROMATIN; HISTONES; MEIOSIS; ADENOSINE triphosphate; EUKARYOTES; MOLECULAR chaperones
- Publication
Scientific Reports, 2014, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep04863