This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huang, Y.
Right arrow Articles by Yuan, Z.-M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, Y.
Right arrow Articles by Yuan, Z.-M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 1999, p. 2986-2997, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role for Caspase-Mediated Cleavage of Rad51 in Induction of Apoptosis by DNA Damage

YinYin Huang,1 Shuji Nakada,1 Takatoshi Ishiko,1 Taiju Utsugisawa,1 Rakesh Datta,1 Surender Kharbanda,1 Kiyotsugu Yoshida,1 Robert V. Talanian,2 Ralph Weichselbaum,3 Donald Kufe,1,* and Zhi-Min Yuan1

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 021151; BASF Bioresearch Corp., Worcester, Massachusetts 016052; and Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 606373

Received 29 July 1998/Returned for modification 18 September 1998/Accepted 15 December 1998

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.


* Corresponding author. Mailing address: Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, MA 02115. Phone: (617) 632-3141. Fax: (617) 632-2934. E-mail: donald_kufe{at}dfci.harvard.edu.


Molecular and Cellular Biology, April 1999, p. 2986-2997, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Bolderson, E., Richard, D. J., Edelmann, W., Khanna, K. K. (2009). Involvement of Exo1b in DNA damage-induced apoptosis. Nucleic Acids Res 37: 3452-3463 [Abstract] [Full Text]  
  • Adimoolam, S., Sirisawad, M., Chen, J., Thiemann, P., Ford, J. M., Buggy, J. J. (2007). HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proc. Natl. Acad. Sci. USA 104: 19482-19487 [Abstract] [Full Text]  
  • Valenti, A., Napoli, A., Ferrara, M. C., Nadal, M., Rossi, M., Ciaramella, M. (2006). Selective degradation of reverse gyrase and DNA fragmentation induced by alkylating agent in the archaeon Sulfolobus solfataricus.. Nucleic Acids Res 34: 2098-2108 [Abstract] [Full Text]  
  • Weinberger, M., Ramachandran, L., Feng, L., Sharma, K., Sun, X., Marchetti, M., Huberman, J. A., Burhans, W. C. (2005). Apoptosis in budding yeast caused by defects in initiation of DNA replication. J. Cell Sci. 118: 3543-3553 [Abstract] [Full Text]  
  • Smith, J. J., Cole, E. S., Romero, D. P. (2004). Transcriptional control of RAD51 expression in the ciliate Tetrahymena thermophila. Nucleic Acids Res 32: 4313-4321 [Abstract] [Full Text]  
  • Chen, F., Arseven, O. K., Cryns, V. L. (2004). Proteolysis of the Mismatch Repair Protein MLH1 by Caspase-3 Promotes DNA Damage-induced Apoptosis. J. Biol. Chem. 279: 27542-27548 [Abstract] [Full Text]  
  • Pati, D., Zhang, N., Plon, S. E. (2002). Linking Sister Chromatid Cohesion and Apoptosis: Role of Rad21. Mol. Cell. Biol. 22: 8267-8277 [Abstract] [Full Text]  
  • Bordone, L., Campbell, C. (2002). DNA Ligase III Is Degraded by Calpain during Cell Death Induced by DNA-damaging Agents. J. Biol. Chem. 277: 26673-26680 [Abstract] [Full Text]  
  • Chen, F., Kamradt, M., Mulcahy, M., Byun, Y., Xu, H., McKay, M. J., Cryns, V. L. (2002). Caspase Proteolysis of the Cohesin Component RAD21 Promotes Apoptosis. J. Biol. Chem. 277: 16775-16781 [Abstract] [Full Text]  
  • Wiese, C., Pierce, A. J., Gauny, S. S., Jasin, M., Kronenberg, A. (2002). Gene Conversion Is Strongly Induced in Human Cells by Double-strand Breaks and Is Modulated by the Expression of BCL-xL. Cancer Res. 62: 1279-1283 [Abstract] [Full Text]  
  • Raderschall, E., Stout, K., Freier, S., Suckow, V., Schweiger, S., Haaf, T. (2002). Elevated Levels of Rad51 Recombination Protein in Tumor Cells. Cancer Res. 62: 219-225 [Abstract] [Full Text]  
  • Vasquez, K. M., Marburger, K., Intody, Z., Wilson, J. H. (2001). Manipulating the mammalian genome by homologous recombination. Proc. Natl. Acad. Sci. USA 98: 8403-8410 [Abstract] [Full Text]  
  • Noah, D. L., Blum, M. A., Sherry, B. (1999). Interferon Regulatory Factor 3 Is Required for Viral Induction of Beta Interferon in Primary Cardiac Myocyte Cultures. J. Virol. 73: 10208-10213 [Abstract] [Full Text]  
  • Bischof, O., Galande, S., Farzaneh, F., Kohwi-Shigematsu, T., Campisi, J. (2001). Selective Cleavage of BLM, the Bloom Syndrome Protein, during Apoptotic Cell Death. J. Biol. Chem. 276: 12068-12075 [Abstract] [Full Text]