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

• DOI: 10.1038/srep04863
• Publication Date: 2014-05-06T10:15:51Z
• 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
• Keywords: Adenosine Triphosphatases; 0301 basic medicine; tRNA Methyltransferases; DNA Repair; DNA Helicases; Nuclear Proteins; Proteins; Article; Chromatin; Cell Line; Nucleosomes; DNA-Binding Proteins; Histones; 03 medical and health sciences; DNA Repair Enzymes; Escherichia coli; Humans; Rad51 Recombinase; Homologous Recombination

AbstractHomologous 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.