TY - JOUR
T1 - Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1
AU - Machida, Shinichi
AU - Takaku, Motoki
AU - Ikura, Masae
AU - Sun, Jiying
AU - Suzuki, Hidekazu
AU - Kobayashi, Wataru
AU - Kinomura, Aiko
AU - Osakabe, Akihisa
AU - Tachiwana, Hiroaki
AU - Horikoshi, Yasunori
AU - Fukuto, Atsuhiko
AU - Matsuda, Ryo
AU - Ura, Kiyoe
AU - Tashiro, Satoshi
AU - Ikura, Tsuyoshi
AU - Kurumizaka, Hitoshi
PY - 2014/5/6
Y1 - 2014/5/6
N2 - 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.
AB - 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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U2 - 10.1038/srep04863
DO - 10.1038/srep04863
M3 - Article
C2 - 24798879
AN - SCOPUS:84900029653
SN - 2045-2322
VL - 4
JO - Scientific Reports
JF - Scientific Reports
M1 - 4863
ER -