Neurochemical Research

, Volume 28, Issue 2, pp 187–194

Role of PARP Under Stress Conditions: Cell Death or Protection?

  • Vincenzo Giuseppe Nicoletti
  • Anna Maria Giuffrida Stella


A great deal of increasing evidence designs PARP as a multifunctional protein implicated in many cellular functions. Much interest is emerging to understand the precise mechanisms by which PARP mediates genome stabilization and protection against damage, as well as its involvement in cell death, either apoptotic or necrotic. Aside from the clearly established role of PARP hyperactivation in necrotic cell death, after excessive DNA damage and energy failure, it appears to be actively involved in the phenomenon of apoptosis. However, its exact role is still controversial. The identification of several enzymes sharing the poly(ADP-ribose) polymerase catalytic domain (PARPs), but with different features and subcellular localization, has opened a new perspective in the field of poly(ADP-ribosyl)ation. The picture of the role of PARP in the control of cell homeostasis became even more complex after demonstration of its implication in the regulation of gene transcription. The notion that energy failure is the sole mechanism by which PARP promotes cell death is therefore under reevaluation.

PARP cell death stress NO neurodegeneration 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lindhal, T., Satoh, M. S., Poirier, G. G., Klungland, A. 1995. Posttranslational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem. Sci. 20:405–411.PubMedGoogle Scholar
  2. 2.
    Simbulan-Rosenthal, C. M. G., Rosenthal, D. S., Hilz, H., Hickey, R., Malkas, L., Applegren, N., Wu, Y., Bers, G., and Smulson, M. 1996. The expression of poly(ADP-ribose) polymerase during differentiation-linked DNA replication reveals that this enzyme is a component of the multiprotein DNA replication complex. Biochemistry 35:622–633.Google Scholar
  3. 3.
    Yakovlev, A. G., Wang, G., Stoica, B. A., Boulares, H. A., Spoonde, A. Y., Yoshihara, K., and Smulson, M. E. 2000. A role of the Ca2+/Mg2+-dependent endonuclease in apoptosis and its inhibition by poly(ADP-ribose) polymerase. J. Biol. Chem. 275: 21302–21308.PubMedGoogle Scholar
  4. 4.
    Bauer, P. I., Chen, H., Kenesi, E., Kenessey, I., Buki, K. G., Kirsten, E., Hakam, A., Hwang, J. I., and Kun, E. 2001. Molecular interactions between poly(ADP-ribose) polymerase (PARP I) and topoisomerase I (Topo I): identification of topology of binding. FEBS Lett. 506:239–242.PubMedGoogle Scholar
  5. 5.
    Gradwohl, G., Menissier De-Murcia, J. M., Molinette, M., Simonin, F., Koken, M., Hoeijimakers, J. H., and De-Murcia, G. 1990. The second zinc finger domain of poly(ADP-ribose) polymerase determines specificity for single-stranded breaks in DNA. Proc. Natl. Acad. Sci. 87:2990–2994.PubMedGoogle Scholar
  6. 6.
    Alvarez-Gonzalez, R. and Mendoza-Alvarez, H. 1995. Dissection of ADP-ribose polymer synthesis into individual steps of initiation, elongation. Biochimie 77:403–407.PubMedGoogle Scholar
  7. 7.
    Alvarez-Gonzalez, R. and Althaus, F. R. 1989. Poly(ADP-ribose) catabolism in mammalian cells exposed to DNA-damaging agents. Mutat. Res. 218:67–74.PubMedGoogle Scholar
  8. 8.
    Berger, N. A. 1985. Poly(ADP-ribose) in the cellular response to DNA damage. Radiat. Res. 101:4–15.PubMedGoogle Scholar
  9. 9.
    Eliasson, M. J. L., Sampei, K., Mandir, A. S., Hurn, P. D., Traystman, R. J., Bao, J., Pieper, A., Wang, Z. O., Dawson, T. M., Snyder, S. H., and Dawson, V. L. 1997. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischaemia. Nat. Med. 3:1089–1095.PubMedGoogle Scholar
  10. 10.
    Ha, H. C. and Snyder, S. H. 2000. Poly (ADP-ribose) polymerase-1 in the nervous system. Neurobiol. Dis. 7:225–239.PubMedGoogle Scholar
  11. 11.
    Plaschke, K., Kopitz, J., Weigand, M. A., Martin, E., and Bardenheuer, H. J. 2000. The neuroprotective effect of cerebral poly(ADP-ribose) polymerase inhibition in a rat model of global ischemia. Neurosci. Lett. 284:109–112.PubMedGoogle Scholar
  12. 12.
    Szabò, C. 1996. DNA strand breakage and activation of the poly-ADP ribosyltransferase: a cytotoxic pathway triggered by peroxinitrite. Free Rad. Biol. Med. 21:855–869.PubMedGoogle Scholar
  13. 13.
    Szabò, A., Hake, P., Salzman, A. L., and Szabò, C. 1998. 3–Aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, improves hemodynamics and prolongs survival in a porcine model of hemorrhagic shock. Shock 10:347–353.PubMedGoogle Scholar
  14. 14.
    Cosi, C., Suzuki, H., Milani, D., Facci, L., Menegazzi, M., Vantini, G., Kanai, Y., and Skaper, S. D. 1994. Poly(ADP-ribose) polymerase early involvement in glutamate-induced neurotoxicity in cultured cerebellar granule cells. J. Neurosci. Res. 39:38–46.PubMedGoogle Scholar
  15. 15.
    Zhang, J., Pieper, A., and Snyder, S. H. 1995. Poly(ADP-ribose)synthetase activation: an early indicator of neurotoxic damage. J. Neurochem. 65:1411–1414.PubMedGoogle Scholar
  16. 16.
    Pieper, A. A., Blackshaw, S., Clements, E. E., Brat, D. J., Krug, D. K., White, A. J., Pinto-Garcia, P., Favit, A., Conover, J. R., Snyder, S. H., and Verma, A. 2000. Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission. Proc. Natl. Acad. Sci. USA 97:1845–1850.PubMedGoogle Scholar
  17. 17.
    Mandir, A. S., Przedborski, S., Jackson-Lewis, V., Wang, Z., Simbulan-Rosenthal, C. M., Smulson, M. E., Hoffmann, B. E., Guastella, D. B., Dawson, V. L., and Dawson, T. M. 1999. Poly(ADP-ribose) polymerase activation mediates 1–methyl-4–phenyl-1,2,3,6–tetrahydropyridine (MPTP)-induced parkinsonism. Proc. Natl. Acad. Sci. USA 96:5774–5779.PubMedGoogle Scholar
  18. 18.
    Cosi, C., Suzuki, H., Skaper, S. D., Milani, D., Facci, L., Menegazzi, M., Vantini, G., Kanai, Y., Degryse, A., Colpaert F., Koek, W., and Marien, M. R. 1997. Poly(ADP-ribose) polymerase (PARP) revisited: a new role for an old enzyme—PARP involvement in neurodegeneration and PARP inhibitors as possible neuroprotective agents. Ann. N.Y. Acad. Sci. 825:366–379.PubMedGoogle Scholar
  19. 19.
    Cosi, C. and Marien, M. 1999. Implication of Poly(ADP-ribose) polymerase (PARP) in neurodegeneration and brain energy metabolism: decreases in mouse brain NAD3 and ATP caused by MPTP are prevented by the PARP inhibitor benzamide. Ann. N.Y. Acad. Sci. 890:227–239.PubMedGoogle Scholar
  20. 20.
    Moroni, F., Meli, E., Peruginelli, F., Chiarugi, A., Cozzi, A., Picca, R., Romagnoli, P., Pellicciari, R., and Pellegrini-Giampietro, D. E. 2001. Poly(ADP-ribose) polymerase inhibitors attenuate necrotic but not apoptotic neuronal death in experimental models of cerebral ischemia. Cell Death Differ. 8:921–932.PubMedGoogle Scholar
  21. 21.
    Strosznajder, J. B., Jesko, H., and Strosznajder, R. P. 2000. Effect of amyloid beta peptide on poly(ADP-ribose) polymerase activity in adult and aged rat hippocampus. Acta Biochim. Pol. 47:847–854.PubMedGoogle Scholar
  22. 22.
    Love, S., Barber, R., and Wilcock, G. K. 1999. Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease. Brain 122:247–253.PubMedGoogle Scholar
  23. 23.
    Le Page, C., Sanceau, J., Drapier, J. C., and Wietzerbin, J. 1998. Inhibitors of ADP-ribosylation impair inducible nitric oxide synthase gene transcription through inhibition of NF-kB activation. Biochem. Biophys. Res. Commun. 243:451–457.PubMedGoogle Scholar
  24. 24.
    Hassa, P. O., Covic, M., Hasan, S., Imhof, R., and Hottiger, M. O. 2001. The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function. J. Biol. Chem. 276:45588–45597.PubMedGoogle Scholar
  25. 25.
    Hassa, P. O. and Hottiger, M. O. 1999. A role of poly (ADP-ribose) polymerase in NF-kappa B transcriptional activation. Biol. Chem. 380:953–959.PubMedGoogle Scholar
  26. 26.
    Gonzalez-Zulueta, M., Ensz, L. M., Mukhina, G., Lebovitz, R. M., Zwacka, R. M., Engelhardt, J. F., Oberley, L. W., Dawson, V. L., and Dawson, T. M. 1998. Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide-mediated neurotoxicity. J. Neurosci. 18:2040–2055.PubMedGoogle Scholar
  27. 27.
    Nicoletti, V. G., Caruso, A., Tendi, E. A., Privitera, A., Console, A., Calabrese, V., Spadaro, F., Ravagna, A., Copani, A., and Giuffrida Stella, A. M. 1998. Effect of nitric oxide synthase induction on the expression of mitochondrial respiratory chain enzyme subunits in mixed cortical and astroglial cell cultures. Biochimie. 80:871–881.PubMedGoogle Scholar
  28. 28.
    Nicoletti, V. G., Spina-Purrello, V., Patti, D., Santangelo, R., and Giuffrida Stella, A. M. 2001. Dual role of PARP after iNOS induction in astroglia cells: proapoptotic or rescuing. J. Neurochem. 77 (suppl. 1):47.Google Scholar
  29. 29.
    Calabrese, V., Copani, A., Testa, D., Ravagna, A., Spadaro, F., Tendi, E., Nicoletti, V. G., and Giuffrida Stella, A. M. 2000. Nitric oxide synthase induction in astroglial cell cultures: effect on heat shock protein 70 synthesis and oxidant/antioxidant balance. J. Neurosci. Res. 60:613–622.PubMedGoogle Scholar
  30. 30.
    Heller, B., Wang, Z. Q., Wagner, E. F., Radons, J., Burkle, A., Fehsel, K., Burkart, V., and Kolb, H. 1995. Inactivation of the poly(ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells J. Biol. Chem. 270:11176–11180.PubMedGoogle Scholar
  31. 31.
    Zhang, J., Dawson, V. L., Dawson, T. M., and Snyder, S. H. 1994. Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263:687–689.PubMedGoogle Scholar
  32. 32.
    Wang, Z. Q., Stingl, L., Morrison, C., Jantsch, M., Los, M., Schulze-Osthoff, E. F., and Wagner, E. W. 1997. PARP is important for genomic stability but dispensable in apoptosis. Genes Dev. 11:2347–2358.PubMedGoogle Scholar
  33. 33.
    Menissier-de Murcia, J., Niedergang, C., Trucco, C., Ricoul, M., Dutrilloux, B., Mark, M., Olivier, F. J., Masson, M., Dierich, A., LeMeur, M., Walztinger, C., Chambon, P., and deMurcia, G. 1997. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc. Natl. Acad. Sci. USA 94:7303–7307.PubMedGoogle Scholar
  34. 34.
    Masutani, M., Nozaki, T., Nakamoto, K., Nakagama, H., Suzuki, H., Kusuoka, O., Tsutsumi, M., and Sugimura, T. 2000. The response of PARP knockout mice against DNA damaging agents. Mut. Res. 462:159–166.Google Scholar
  35. 35.
    Dulic, A., Bates, P. A., Zhang, X., Martin, S. R., Freemont, P. S., Lindahl, T., and Barnes, D. E. 2001. BRCT domain interactions in the heterodimeric DNA repair protein XRCC1–DNA ligase III. Biochemistry 40:5906–5913.PubMedGoogle Scholar
  36. 36.
    Marintchev, A., Robertson, A., Dimitriadis, E. K., Prasad, R., Wilson, S. H., and Mullen, G. P. 2000. Domain specific interaction in the XRCC1–DNA polymerase beta complex. Nucl. Acids Res. 28:2049–2059.PubMedGoogle Scholar
  37. 37.
    Trucco, C., Oliver, F. J., de Murcia, G., and Menissier-de Murcia, J. 1998. DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines. Nucl. Acids Res. 26:2644–2649.PubMedGoogle Scholar
  38. 38.
    Pieper, A. A., Brat, D. J., Krug, D. K., Watkins, C. C., Gupta, A., Blackshaw, S., Verma, A., Wang, Z. Q., and Snyder, S. H. 1999. Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes. Proc. Natl. Acad. Sci. USA 96:3059–3064.PubMedGoogle Scholar
  39. 39.
    Bursztajn, S., Feng, J.-J., Berman, S. A., and Nanda, A. 2000. Poly ADP-ribose polymerase induction is an early signal of apoptosis in human neuroblastoma. Molec. Brain Res. 76:363–376.PubMedGoogle Scholar
  40. 40.
    Simbulan-Rosenthal, C. M., Rosenthal, D. S., Iyer, S., Boulares, A. H., and Smulson, M. E. 1998. Transient Poly(ADP-ribosyl)ation of nuclear proteins and role of poly(ADP-ribose) polymerase in the early stage of apoptosis J. Biol. Chem. 273: 13703–13712.PubMedGoogle Scholar
  41. 41.
    Le Rhun, Y., Kirkland, J. B., and Shah, G. M. 1998. Cellular responses to DNA damage in the absence of poly(ADP-ribose) polymerase. Biochem. Biophys. Res. Commun. 245:1–10.PubMedGoogle Scholar
  42. 42.
    Boulares, H. A., Yakovlev, A. G., Ivanova, V., Stoica, B. A., Wang, G., Iyer, S., and Smulson, M. 1999. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. J. Biol. Chem. 274:22932–22940.PubMedGoogle Scholar
  43. 43.
    Ha, H. C. and Snyder, S. H. 1999. Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc. Natl. Acad. Sci. USA 23:13978–13982.Google Scholar
  44. 44.
    Halappanavar, S. S., Le Rhun, Y., Mounir, S., Martins, L. M., Huoti, J., Earnshaw, W. C., and Shah, G. M. 1999. Survival and proliferation of cells expressing caspase-uncleavable poly(ADP-ribose) polymerase in response to death-inducing DNA damage by an alkylating agent. J. Biol. Chem. 274:37097–37104.PubMedGoogle Scholar
  45. 45.
    Fujimura, M., Morita-Fujimura, Y., Noshita, N., Yoshimoto, T., and Chan, P. H. 2000. Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice. Brain Res. 869:105–111.PubMedGoogle Scholar
  46. 46.
    Whalen, M. J., Clark, R. S., Dixon, C. E., Robichaud, P., Marion, D. W., Vagni, V., Graham, S. H., Stachlewitz, R., Szabo, C., and Kochanek, P. M. 1999. Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase, J. Cereb. Blood Flow Metab. 19:835–842.PubMedGoogle Scholar
  47. 47.
    Bolaños, J. P., Heales, S. J., Peuchen, S., Barker, J. E., Land, J. M., and Clark, J. B. 1996. Nitric oxide-mediated mitochondrial damage: a potential neuroprotective role for glutathione. Free Radic. Biol. Med. 21:995–1001.PubMedGoogle Scholar
  48. 48.
    Agarwal, M. L., Agarwal, A., Taylor, W. R., Wang, Z. Q., Wagner, E. F., and Stark, G. R. 1997. Defective induction but normal activation and function of p53 in mouse cells lacking poly(ADP-ribose) polymerase. Oncogene 15:1035–1041.PubMedGoogle Scholar
  49. 49.
    Wang, X., Ohnishi, K., Takahashi, A., and Ohnishi, T. 1998. Poly(ADP-ribosyl)ation is required for p53–dependent signal transduction induced by radiation. Oncogene 17:2819–2825.PubMedGoogle Scholar
  50. 50.
    Whitacre, C. M., Hashimoto, H., Tsai, M. L., Chatterjee, S., Berger, S. J., and Berger, N. A. 1995. Involvement of NAD-poly(ADP-ribose) metabolism in p53 regulation and its consequences. Cancer Res. 55:3697–3701.PubMedGoogle Scholar
  51. 51.
    Smulson, M. E., Simbulan-Rosenthal, C. M., Boulares, A. H., Yakovlev, A., Stoica, B., Iyer, S., Luo, R., Haddad, B., Wang, Z. Q., Pang, T., Jung, M., Dritschilo, A., and Rosenthal, D. S. 2000. Roles of poly(ADP-ribosyl)ation and PARP in apoptosis, DNA repair, genomic stability and functions of p53 and E2f-1. Advan. Enzyme Regul. 40:183–215.Google Scholar
  52. 52.
    Cross, S. M., Sanchez, C. A., Morgan, C. A., Schimke, M. K., Ramel, S., Idzerda, R. L., Raskind, W. H., and Reid, B. J. 1995. A p53–dependent mouse spindle checkpoint. Science 267:1353–1356.PubMedGoogle Scholar
  53. 53.
    Fukasawa, K., Choi, T., Kuriyama, R., Rulog, S., and Vande Woude, G. 1996. Abnormal centrosome amplification in the absence of p53. Science 271:1744–1747.PubMedGoogle Scholar
  54. 54.
    Simbulan-Rosenthal, C. M., Haddad, B. R., Rosenthal, D. S., Weaver, Z., Coleman, A., Luo, R., Young, H. M., Wang, Z., Ried, T., and Smulson, M. E. 1999. Chromosomal aberrations in PARP-/-mice: Genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA. Proc. Natl. Acad. Sci. USA 96:13191–13196.PubMedGoogle Scholar
  55. 55.
    Hough, C. J. and Smulson, M. E. 1994. Association of poly (adenosine diphosphate ribosylated) nucleosome with transcriptionally active and inactive regions of chromatin. Biochemistry 23:5016–5023.Google Scholar
  56. 56.
    Bauer, P. I., Kirsten, E., Young, L. J. T., Varadi, G., Csonka, E., Buki, K. G., Mikala, G., Hu, R., Comstock, J. A., Mendeleyev, J., Hakam, A., and Kun, E. 1996. Modification of growth related enzymatic pathways and apparent loss of tumorigenicity of a Ras-transformed bovine endothelial cell line by treatment with 5–iodo-6–amino-1,2–benzopyrone. Int. J. Oncol. 8:239–252.Google Scholar
  57. 57.
    Nagao, M., Nakayasu, M., Aonuma, S., Shima, H., and Sugimura, T. 1991. Loss of amplified genes by poly(ADP-ribose) polymerase inhibitors. Enviorn. Health Perspect. 93:169–174.Google Scholar
  58. 58.
    Hauschildt, S., Scheipers, P., Bessler, W. G., and Mulsch, A. 1992. Induction of nitric oxide synthase in L929 cells by tumor-necrosis factor alpha is prevented by inhibitors of poly(ADP-ribose) polymerase. Biochem. J. 288:255–260.PubMedGoogle Scholar
  59. 59.
    Meisterernst, M., Stelzer, G., Roeder, R. G. 1997. Poly(ADP-ribose) polymerase enhances activator-dependent transcription in vitro. Proc. Natl. Acad. Sci. USA 94:2261–2265.PubMedGoogle Scholar
  60. 60.
    Oei, S., Griesenbeck, J., Schweiger, M., and Ziegler, M. 1998. Regulation of RNA polymerase II-dependent transcription by poly(ADP-ribosyl)ation of transcription factors. J. Biol. Cem. 273:31644–31647.Google Scholar
  61. 61.
    Ullrich, O., Diestel, A., Eyüpoglu, I. Y., and Nitsch, R. 2001. Regulation of microglial expression of integrins by poly(ADP-ribose) polymerase-1. Nat. Cell Biol. 3:1035–1042.PubMedGoogle Scholar
  62. 62.
    Vaziri, H., West, M., Allsop, R., Davison, T., Wu, Y., Arrow-smith, C., Poirier, G., and Benchimol, S. 1997. ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J. 16:6018–6033.PubMedGoogle Scholar
  63. 63.
    Simbulan-Rosenthal, C. M., Rosenthal, D. S., and Smulson, M. E. 1999. Poly(ADP-ribosyl)ation of p53 during apoptosis in human osteosarcoma cells. Cancer Res. 59:2190–2194.PubMedGoogle Scholar
  64. 64.
    Oliver, F. J., Menissier-de Murcia, J., Nacci, C., Decker, P., Andriantsitohaina, R., Muller, S., de la Rubia, G., Stoclet, J. C., and de Murcia, G. 1999. Resistance to endotoxic shock as consequence of defective NF-kB activation in poly(ADP-ribose) polymerase-1 deficient mice. EMBO J. 18:4446–4454.PubMedGoogle Scholar
  65. 65.
    Ha, H. C., Hester, L. D., and Snyder, S. H. 2002. Poly(ADP-ribose) polymerase-1 dependence of stress-induced transcription factors and associated gene expression in glia. Proc. Natl. Acad. Sci. USA 99:3270–3275.PubMedGoogle Scholar
  66. 66.
    Amè, J., Rolli, V., Schreiber, V., Niedergang, C., Apiou, F., Decker, P., Muller, S., Hoger, T., de Murcia, J., and de Murcia, G. 1999. PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J. Biol. Chem. 274:17860–17868.PubMedGoogle Scholar
  67. 67.
    Schreiber, V., Amè, J. C., Dolle, P., Schultz, I., Rinaldi, B., Fraulob, V., Menissier-de Murcia, J., and de Murcia, G. 2002. poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. J. Biol. Chem. 277:23028–23036.PubMedGoogle Scholar
  68. 68.
    Smith, S. 2001. The world according to PARP. Trends Biochem. Sci. 19:172–176.Google Scholar
  69. 69.
    Smith, S. and de Lange, T. 2000. Tankirase promotes telomere elongation in human cells. Curr. Biol. 10:1299–1302.PubMedGoogle Scholar
  70. 70.
    Lyons, R. J., Deane, R., Lynch, D. K., Ye, Z. S., Sanderson, G. M., Eyre, H. J., Sutherland, G. R., and Daly, R. J. 2001. Identification of a novel human Tankyrase through its interaction with the adaptor protein Grb14. J. Biol. Chem. 276:17172–17180.PubMedGoogle Scholar
  71. 71.
    Kaminker, P. G., Kim, S. H., Taylor, R. D., Zebarjadian, Y., Funk, W. D., Morin, G. B., Yaswen, P., and Campisi, J. 2001. TANK-2, a new TRF1 associated poly(ADP-ribose) polymerase causes rapid induction of cell death upon overexpression. J. Biol. Chem. 276:35891–35899.PubMedGoogle Scholar
  72. 72.
    Johansson, M. 1999. A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly(ADP-ribose) polymerase homologues. Genomics 57:442–445.PubMedGoogle Scholar
  73. 73.
    Sallmann, F. R., Momchil, D. V., Wang, Z., and Poirier, G. G. 2000. Characterization of sPARP-1: An alternative product of the PARP-1 gene with poly(ADP-ribose) polymerase activity independent of DNA strand breaks. J. Biol. Chem. 275:15504–15511.PubMedGoogle Scholar
  74. 74.
    Kickhoefer, V. A., Siva, A. C., Kedersha, N. L., Inman, E. M., Ruland, C., Streuli, M., Rome, L. H. 1999. The 193–kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase. J. Cell Biol. 146:917–928.PubMedGoogle Scholar
  75. 75.
    Simbulan-Rosenthal, C. M., Ly, D. H., Rosenthal, D. S., Konopka, G., Luo, R., Wang, Z., Schultz, P. G., and Smulson, M. E. 2000. Misregulation of gene expression in primary fibroblast lacking poly(ADP-ribose) polymerase. Proc. Natl. Acad. Sci. USA 97: 11274–11279.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Vincenzo Giuseppe Nicoletti
    • 1
  • Anna Maria Giuffrida Stella
    • 1
  1. 1.Department of Chemical Sciences, Section of Biochemistry and Molecular BiologyUniversity of CataniaCataniaItaly

Personalised recommendations