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Importance of Poly(ADP-ribose) Polymerase and Its Cleavage in Apoptosis
Open accessAbstract
We have studied the apoptotic response of poly(ADP-ribose) polymerase (PARP)-/- cells to different inducers and the consequences of the expression of an uncleavable mutant of PARP on the apoptotic process. The absence of PARP drastically increases the sensitivity of primary bone marrow PARP-/- cells to apoptosis induced by an alkylating agent but not by a topoisomerase I inhibitor CPT-11 or by interleukin-3 removal. cDNA of wild type or of an uncleavable PARP mutant (D214A-PARP) has been introduced into PARP-/- fibroblasts, which were exposed to anti-CD95 or an alkylating agent to induce apoptosis. The expression of D214A-PARP results in a significant delay of cell death upon CD95 stimulation. Morphological analysis shows a retarded cell shrinkage and nuclear condensation. Upon treatment with an alkylating agent, expression of wild-type PARP cDNA into PARP-deficient mouse embryonic fibroblasts results in the restoration of the cell viability, and the D214A-PARP mutant had no further effect on cell recovery. In conclusion, PARP-/- cells are extremely sensitive to apoptosis induced by triggers (like alkylating agents), which activates the base excision repair pathway of DNA, and the cleavage of PARP during apoptosis facilitates cellular disassembly and ensures the completion and irreversibility of the process.
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Cited by
FORTINI, P., & DOGLIOTTI, E. (2007) · DNA Repair · doi:10.1016/j.dnarep.2006.10.008 · Cited by 318
Poly(ADP-ribose) signaling in cell death
Virág, L., Robaszkiewicz, A., Rodriguez-Vargas, J. M., & Oliver, F. J. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.007 · Cited by 273
Self-citationBiasutto, L., Chiechi, A., Couch, R., Liotta, L. A., & Espina, V. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.05.005 · Cited by 126
Storr, H. L., Kind, B., Parfitt, D. A., Chapple, J. P., Lorenz, M., Koehler, K., Huebner, A., & Clark, A. J. L. (2009) · Molecular Endocrinology · doi:10.1210/me.2009-0056 · Cited by 84
Zhang, D., Lu, C., Yu, Z., Wang, X., Yan, L., Zhang, J., Li, H., Wang, J., & Wen, A. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/6851464 · Cited by 55
Metadata
- Authors
- Oliver, F. J., de la Rubia, G., Rolli, V., Ruiz-Ruiz, M. C., de Murcia, G., & Murcia, J. M.-D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 273
- Issue
- 50
- Pages
- 33533-33539
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2127429864
- Cited by
- 754
- References
- 0
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Oliver, F. J., de la Rubia, G., Rolli, V., Ruiz-Ruiz, M. C., de Murcia, G., & Murcia, J. M.-D. (1998). Importance of Poly(ADP-ribose) Polymerase and Its Cleavage in Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.50.33533
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