Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA damage.
Journal Formal name:Molecular and cellular biology
Abbreviation:Mol Cell Biol
ISSN code:02707306/02707306
Domestic / ForeginForegin
Volume, Issue, Page 19(4),pp.2986-2997
Author and coauthor Huang Y, Nakada S, Ishiko T, Utsugisawa T, Datta R, Kharbanda S, Yoshida K, Talanian R V, Weichselbaum R, Kufe D, Yuan Z M
Publication date 1999/04
Summary 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