ウツギサワ　タイジユ   UTSUGISAWA Taijiyu   槍澤　大樹    所属   医学部 医学科（東京女子医科大学病院）    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA damage.
掲載誌名	正式名：Molecular and cellular biology 略　 称：Mol Cell Biol ISSNコード：02707306/02707306
掲載区分	国外
巻・号・頁	19(4),pp.2986-2997
著者・共著者	Huang Y, Nakada S, Ishiko T, Utsugisawa T, Datta R, Kharbanda S, Yoshida K, Talanian R V, Weichselbaum R, Kufe D, Yuan Z M
発行年月	1999/04
概要	We report here that the Rad51 recombinase is cleaved in mammalian cells during the induction of apoptosis by ionizing radiation (IR) exposure. The results demonstrate that IR induces Rad51 cleavage by a caspase-dependent mechanism. Further support for involvement of caspases is provided by the finding that IR-induced proteolysis of Rad51 is inhibited by Ac-DEVD-CHO. In vitro studies show that Rad51 is cleaved by caspase 3 at a DVLD/N site. Stable expression of a Rad51 mutant in which the aspartic acid residues were mutated to alanines (AVLA/N) confirmed that the DVLD/N site is responsible for the cleavage of Rad51 in IR-induced apoptosis. The functional significance of Rad51 proteolysis is supported by the finding that, unlike intact Rad51, the N- and C-terminal cleavage products fail to exhibit recombinase activity. In cells, overexpression of the Rad51(D-A) mutant had no effect on activation of caspase 3 but did abrogate in part the apoptotic response to IR exposure. We conclude that proteolytic inactivation of Rad51 by a caspase-mediated mechanism contributes to the cell death response induced by DNA damage.
DOI	10.1128/mcb.19.4.2986
PMID	10082566