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UTSUGISAWA Taiju
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Associate Professor |
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| 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 / Foregin | Foregin |
| 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 |