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	2018/02
形態種別	学術論文
査読	査読あり
標題	The deubiquitylating enzyme UCHL3 regulates Ku80 retention at sites of DNA damage
執筆形態	共著
掲載誌名	Scientific Reports
掲載区分	国外
出版社・発行元	SPRINGER NATURE
巻・号・頁	8,pp.17891
総ページ数	15
担当区分	筆頭著者,責任著者
国際共著	国際共著
著者・共著者	Ryotaro Nishi, Paul W. G. Wijnhoven, Yusuke Kimura, Misaki Matsui, Rebecca Konietzny, Qian Wu, Keisuke Nakamura, Tom L. Blundell, and Benedikt M. Kessler
概要	Non-homologous end-joining (NHEJ), which can promote genomic instability when dysfunctional, is a major DNA double-strand break (DSB) repair pathway. Although ubiquitylation of the core NHEJ factor, Ku (Ku70-Ku80), which senses broken DNA ends, is important for its removal from sites of damage upon completion of NHEJ, the mechanism regulating Ku ubiquitylation remains elusive. We provide evidence showing that the ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) interacts with and directly deubiquitylates one of the Ku heterodimer subunits, Ku80. Additionally, depleting UCHL3 resulted in reduced Ku80 foci formation, Ku80 binding to chromatin after DSB induction, moderately sensitized cells to ionizing radiation and decreased NHEJ efficiencies. Mechanistically, we show that DNA damage induces UCHL3 phosphorylation, which is dependent on ATM, downstream NHEJ factors and UCHL3 catalytic activity. Furthermore, this phosphorylation destabilizes UCHL3, despite having no effect on its catalytic activity. Collectively, these data suggest that UCHL3 facilitates cellular viability after DSB induction by antagonizing Ku80 ubiquitylation to enhance Ku80 retention at sites of damage.
DOI	https://doi.org/10.1038/s41598-018-36235-0
論文（査読付）ファイル	DOWNLOAD