ニシ　リョウタロウ   西　良太郎    所属   応用生物学部 応用生物学科    職種   准教授
言語種別	英語
発行・発表の年月	2020/06
形態種別	学術論文
査読	査読あり
標題	USP42 enhances homologous recombination repair by promoting R-loop resolution with a DNA-RNA helicase DHX9
執筆形態	共著
掲載誌名	Oncogenesis
掲載区分	国外
出版社・発行元	SPRINGER NATURE
巻・号・頁	9,pp.60
総ページ数	13
担当区分	最終著者,責任著者
著者・共著者	Misaki Matsui, Ryo Sakasai, Masako Abe, Yusuke Kimura, Shoki Kajita, Wakana Torii, Yoko Katsuki, Masamichi Ishiai, Kuniyoshi Iwabuchi, Minoru Takata and Ryotaro Nishi
概要	The nucleus of mammalian cells is compartmentalized by nuclear bodies such as nuclear speckles, however, involvement of nuclear bodies, especially nuclear speckles, in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, identified transcription-related nuclear speckle factors as potential HR regulators. Among the top hits, we provide evidence showing that USP42, which is a hitherto unidentified nuclear speckles protein, promotes HR by facilitating BRCA1 recruitment to DSB sites and DNA-end resection. We further showed that USP42 localization to nuclear speckles is required for efficient HR. Furthermore, we established that USP42 interacts with DHX9, which possesses DNA-RNA helicase activity, and is required for efficient resolution of DSB-induced R-loop. In conclusion, our data propose a model in which USP42 facilitates BRCA1 loading to DSB sites, resolution of DSB-induced R-loop and preferential DSB repair by HR, indicating the importance of nuclear speckle mediated regulation of DSB repair.
DOI	https://doi.org/10.1038/s41389-020-00244-4
論文（査読付）ファイル	DOWNLOAD