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

被引:32
|
作者
Machida, Shinichi [1 ]
Takaku, Motoki [1 ]
Ikura, Masae [2 ]
Sun, Jiying [3 ]
Suzuki, Hidekazu [3 ]
Kobayashi, Wataru [1 ]
Kinomura, Aiko [3 ]
Osakabe, Akihisa [1 ]
Tachiwana, Hiroaki [1 ]
Horikoshi, Yasunori [3 ]
Fukuto, Atsuhiko [3 ]
Matsuda, Ryo [2 ]
Ura, Kiyoe [4 ]
Tashiro, Satoshi [3 ]
Ikura, Tsuyoshi [2 ]
Kurumizaka, Hitoshi [1 ]
机构
[1] Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, Tokyo 1628480, Japan
[2] Kyoto Univ, Dept Mutagenesis, Div Chromatin Regulatory Network, Radiat Biol Ctr,Sakyo Ku, Kyoto 6068501, Japan
[3] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Cellular Biol, Minami Ku, Hiroshima 7348553, Japan
[4] Osaka Univ, Div Gene Therapy Sci, Grad Sch Med, Suita, Osaka 5650871, Japan
来源
SCIENTIFIC REPORTS | 2014年 / 4卷
关键词
NUCLEOSOME ASSEMBLY PROTEIN-1; DNA-DAMAGE; CHAPERONES; REPAIR; BINDING; VARIANT; DIMER; DYNAMICS; YEAST; NASP;
D O I
10.1038/srep04863
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:11
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