Natural Inhibitors of Poly(ADP-ribose) Polymerase-1

Molecular Neurobiology - Tập 46 - Trang 55-63 - 2012
Marek Banasik1, Todd Stedeford2, Robert P. Strosznajder3
1Institute of Public Health and Environmental Protection, Warsaw, Poland
2Albemarle Corporation, Baton Rouge, USA
3Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

Tóm tắt

Poly(ADP-ribose) polymerases (PARPs) are enzymes that catalyze the transfer of ADP-ribose units from β-nicotinamide adenine dinucleotide (NAD+) to acceptor proteins. PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death. The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA. Upon binding, PARP-1 activity increases rapidly and cleaves NAD+ into ADP-ribose and nicotinamide. Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD+ and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively. Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders. Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research. Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation. This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1. Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors. With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.

Tài liệu tham khảo

D'Amours D, Desnoyers S, D'Silva I, Poirier GG (1999) Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J 342:249–268 Hayaishi O, Ueda K (1982) Poly- and mono(ADP-ribosyl)ation reactions. Their significance in molecular biology. In: Hayaishi O, Ueda K (eds) ADP-ribosylation reactions. Biology and medicine. Academic Press, New York, London, pp 3–16 Schreiber V, Dantzer F, Amé J-C, de Murcia G (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 7:517–528 Kauppinen TM (2007) Multiple roles for poly(ADP-ribose)polymerase-1 in neurological disease. Neurochem Int 50:954–958 Skaper SD (2003) Poly(ADP-Ribose) polymerase-1 in acute neuronal death and inflammation. A strategy for neuroprotection. Ann N Y Acad Sci 993:217–228 Koh DW, Dawson TM, Dawson VL (2005) Poly(ADP-ribosyl)ation regulation of life and death in the nervous system. Cell Mol Life Sci 62:760–768 Kauppinen TM, Swanson RA (2007) The role of poly(ADP-ribose) polymerase-1 in CNS disease. Neuroscience 145:1267–1272 Altmeyer M, Hottiger MO (2009) Poly(ADP-ribose) polymerase 1 at the crossroad of metabolic stress and inflammation in aging. Aging (Albany NY) 1:458–469 Kauppinen TM, Suh SW, Berman AE, Hamby AM, Swanson RA (2009) Inhibition of poly(ADP-ribose) polymerase suppresses inflammation and promotes recovery after ischemic injury. J Cereb Blood Flow Metab 29:820–829 Ha HC, Snyder SH (1999) Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci USA 96:13978–13982 Ying W, Alano CC, Garnier P, Swanson RA (2005) NAD+ as a metabolic link between DNA damage and cell death. J Neurosci Res 79:216–223 Andrabi SA, Dawson TM, Dawson VL (2008) Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann N Y Acad Sci 1147:233–241 David KK, Andrabi SA, Dawson TM, Dawson VL (2009) Parthanatos, a messenger of death. Front Biosci 14:1116–1128 Strosznajder RP, Jesko H, Dziewulska J (2005) Effect of carvedilol on neuronal survival and poly(ADP-ribose) polymerase activity in hippocampus after transient forebrain ischemia. Acta Neurobiol Exp (Wars) 65:137–143 Strosznajder R, Gajkowska B (2006) Effect of 3-aminobenzamide on Bcl-2, Bax and AIF localization in hippocampal neurons altered by ischemia-reperfusion injury. The immunocytochemical study. Acta Neurobiol Exp (Wars) 66:15–22 Su P-H, Takehashi M, Tanaka S, Banasik M, Stedeford T, Ueda K, Muro-Cacho C, Harbison RD (2003) Hepatocellular accumulation of poly(ADP-ribose) in male ICR mice treated with a necrogenic dose of carbon tetrachloride. Res Commun Mol Pathol Pharmacol 113–114:171–179 Banasik M, Stedeford T, Ueda K, Muro-Cacho C, Su P-H, Tanaka S, Harbison RD (2004) Hepatoprotective effects of 6(5H)-phenanthridinone from chemical-induced centrilobular necrosis. Res Commun Mol Pathol Pharmacol 115–116:15–20 Banasik M, Stedeford T, Strosznajder RP, Takehashi M, Tanaka S, Ueda K (2011) Inhibition of poly(ADP-ribose) polymerase-1 attenuates the toxicity of carbon tetrachloride. J Enzyme Inhib Med Chem 26:883–889 Banasik M, Ueda K (1994) Inhibitors and activators of ADP-ribosylation reactions. Mol Cell Biochem 138:185–197 Purnell MR, Whish WJD (1980) Novel inhibitors of poly(ADP-ribose) synthetase. Biochem J 185:775–777 Rankin PW, Jacobson EL, Benjamin RC, Moss J, Jacobson MK (1989) Quantitative studies of inhibitors of ADP-ribosylation in vitro and in vivo. J Biol Chem 264:4312–4317 Banasik M, Komura H, Shimoyama M, Ueda K (1992) Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase. J Biol Chem 267:1569–1575 Endres M, Wang Z-Q, Namura S, Waeber C, Moskowitz MA (1997) Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase. J Cereb Blood Flow Metab 17:1143–1151 Takahashi K, Greenberg JH, Jackson P, Maclin K, Zhang J (1997) Neuroprotective effects of inhibiting poly(ADP-ribose) synthetase on focal cerebral ischemia in rats. J Cereb Blood Flow Metab 17:1137–1142 Strosznajder RP, Gadamski R, Czapski GA, Jesko H, Strosznajder JB (2003) Poly(ADP-ribose) polymerase during reperfusion after transient forebrain ischemia. Its role in brain edema and cell death. J Mol Neurosci 20:61–72 Strosznajder RP, Walski M (2004) Effects of 3-aminobenzamide on ultrastructure of hippocampal CA1 layer after global ischemia in gerbils. J Physiol Pharmacol 55:127–133 Drel VR, Lupachyk S, Shevalye H, Vareniuk I, Xu W, Zhang J, Delamere NA, Shahidullah M, Slusher B, Obrosova IG (2010) New therapeutic and biomarker discovery for peripheral diabetic neuropathy: PARP inhibitor, nitrotyrosine, and tumor necrosis factor-α. Endocrinology 151:2547–2555 Pandya KG, Patel MR, Lau-Cam CA (2010) Comparative study of the binding characteristics to and inhibitory potencies towards PARP and in vivo antidiabetogenic potencies of taurine, 3-aminobenzamide and nicotinamide. J Biomed Sci 17:S16 Iwashita A, Mihara K, Yamazaki S, Matsuura S, Ishida J, Yamamoto H, Hattori K, Matsuoka N, Mutoh S (2004) A new poly(ADP-ribose) polymerase inhibitor, FR261529 [2-(4-chlorophenyl)-5-quinoxalinecarboxamide], ameliorates methamphetamine-induced dopaminergic neurotoxicity in mice. J Pharmacol Exp Ther 310:1114–1124 Adamczyk A, Czapski GA, Jęśko H, Strosznajder RP (2005) Non-Aβ component of Alzheimer's disease amyloid and amyloid beta peptides evoked poly(ADP-ribose) polymerase-dependent release of apoptosis-inducing factor from rat brain mitochondria. J Physiol Pharmacol 56:5–13 Abeti R, Abramov AY, Duchen MR (2011) β-Amyloid activates PARP causing astrocytic metabolic failure and neuronal death. Brain 134:1658–1672 Kauppinen TM, Suh SW, Higashi Y, Berman AE, Escartin C, Won SJ, Wang C, Cho S-H, Gan L, Swanson RA (2011) Poly(ADP-ribose)polymerase-1 modulates microglial responses to amyloid β. J Neuroinflammation 8:152. doi:10.1186/1742-2094-8-152 Chalmers AJ (2009) The potential role and application of PARP inhibitors in cancer treatment. Br Med Bull 89:23–40 Javle M, Curtin NJ (2011) The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy. Ther Adv Med Oncol 3:257–267 Alano CC, Kauppinen TM, Valls AV, Swanson RA (2006) Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci USA 103:9685–9690 Szabo C, Pacher P, Swanson RA (2006) Novel modulators of poly(ADP-ribose) polymerase. Trends Pharmacol Sci 27:626–630 Mabley JG, Wallace R, Pacher P, Murphy K, Szabó C (2007) Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D. Int J Mol Med 19:947–952 Shall S (1983) ADP-ribosylation, DNA repair, cell differentiation and cancer. In: Miwa M, Hayaishi O, Shall S, Smulson M, Sugimura T (eds) ADP-ribosylation, DNA repair and cancer. Japan Sci Soc Press, Tokyo/VNU Science Press BV, Utrecht, pp 3–25 Hayaishi O, Ueda K (1974) On the roles of DNA and DNA fragments in the enzymic synthesis and degradation of poly(ADP-ribose). In: Harris M (ed) Fogarty International Center Proceedings No 26: Poly(ADP-Ribose). Bethesda, MD, pp 69–76 Müller WEG, Zahn RK (1975) Influence of agents that act on DNA and RNA synthesis on the activity of poly(ADP-Rib) polymerase. Experientia 31:1014–1015 Müller WEG, Rohde HJ, Steffen R, Maidhof A, Lachmann M, Zahn RK, Umezawa H (1975) Influence of formycin B on polyadenosine diphosphoribose synthesis in vitro and in vivo. Cancer Res 35:3673–3681 Ito S, Shizuta Y, Hayaishi O (1979) Purification and characterization of poly(ADP-ribose) synthetase from calf thymus. J Biol Chem 254:3647–3651 Benjamin RC, Cook PF, Jacobson MK (1985) Kinetic mechanism of poly(ADP-ribose) polymerase. In: Althaus FR, Hilz H, Shall S (eds) ADP-ribosylation of proteins. Springer-Verlag, Berlin, pp 93–97 Niedergang C, Okazaki H, Mandel P (1979) Properties of purified calf thymus poly(adenosine diphosphate ribose) polymerase. Comparison of the DNA-independent and the DNA-dependent enzyme. Eur J Biochem 102:43–57 Römer V, Lambrecht J, Kittler M, Hilz H (1968) Identity of nuclear NAD nucleosidase with a polyADP-ribose forming enzyme in Ehrlich ascites tumor cells. Hoppe-Seyler's Z Physiol Chem 349:109–112 Clark JB, Ferris GM, Pinder S (1971) Inhibition of nuclear NAD nucleosidase and poly ADP-ribose polymerase activity from rat liver by nicotinamide and 5'-methyl nicotinamide. Biochim Biophys Acta 238:82–85 Ueda K, Miyakawa N, Hayaishi O (1972) Poly(ADP-ribose) biosynthesis and degradation in rat liver chromatin. Hoppe-Seyler's Z Physiol Chem 353:844–845 Stone PR, Shall S (1973) Poly(adenosine diphosphoribose) polymerase in mammalian nuclei. Characterization of the activity in mouse fibroblasts (LS cells). Eur J Biochem 38:146–152 Ohgushi H, Yoshihara K, Kamiya T (1980) Bovine thymus poly(adenosine diphosphate ribose) polymerase. Physical properties and binding to DNA. J Biol Chem 255:6205–6211 Moonen HJJ, Geraets L, Vaarhorst A, Bast A, Wouters EFM, Hageman GJ (2005) Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary epithelial cells. Biochem Biophys Res Commun 338:1805–1810 Banasik M, Komura H, Ueda K (1990) Inhibition of poly(ADP-ribose) synthetase by unsaturated fatty acids, vitamins and vitamin-like substances. FEBS Lett 263:222–224 Tanaka Y, Matsunami N, Yoshihara K (1981) Inhibition of ADP-ribosylation of histone by diadenosine 5', 5'''-p1, p4-tetraphosphate. Biochem Biophys Res Commun 99:837–843 Suzuki H, Tanaka Y, Buonamassa DT, Farina B, Leone E (1987) Inhibition of ADP-ribosylation of histone H1 by analogs of diadenosine 5', 5'''-p1, p4-tetraphosphate. Mol Cell Biochem 74:17–20 Kun E, Kirsten E, Mendeleyev J, Ordahl CP (2004) Regulation of the enzymatic catalysis of poly(ADP-ribose) polymerase by dsDNA, polyamines, Mg2+, Ca2+, histones H1 and H3, and ATP. Biochemistry 43:210–216 Leone E, Suzuki H, Farina B, Pivazian AD, Karpeisky MYA (1985) Inhibition of ADP-ribosylation reaction by 2',5'-oligoadenylates. In: Althaus FR, Hilz H, Shall S (eds) ADP-ribosylation of proteins. Springer-Verlag, Berlin, pp 106–110 Pivazian AD, Suzuki H, Vartanian AA, Zhelkovsky AM, Farina B, Leone E, Karpeisky MYa (1984) Regulation of poly(ADP-ribose) transferase activity by 2',5'-oligoadenylates. Biochem Int 9:143–152 Tseng A Jr, Lee WM, Jakobovits EB, Kirsten E, Hakam A, McLick J, Buki K, Kun E (1987) Prevention of tumorigenesis of oncogene-transformed rat fibroblasts with DNA site inhibitors of poly(ADP ribose) polymerase. Proc Natl Acad Sci USA 84:1107–1111, Erratum in: Proc Natl Acad Sci USA 84:3037 Fujimura S, Hasegawa S, Shimizu Y, Sugimura T (1967) Polymerization of the adenosine 5'-diphosphate-ribose moiety of nicotinamide-adenine dinucleotide by nuclear enzyme. I. Enzymatic reactions. Biochim Biophys Acta 145:247–259 Sugimura T, Fujimura S, Hasegawa S, Shimizu Y, Okuyama H (1968) Polymerization of ADPR moiety of NAD by nuclear enzyme preparation. J Vitaminol (Kyoto) 14:135–142 Nishizuka Y, Ueda K, Nakazawa K, Reeder RH, Honjo T, Hayaishi O (1968) Poly adenosine diphosphate ribose synthesis and nicotinamide adenine dinucleotide transglycosidases. J Vitaminol (Kyoto) 14:143–152 Preiss J, Schlaeger R, Hilz H (1971) Specific inhibition of poly ADPRibose polymerase by thymidine and nicotinamide in HeLa cells. FEBS Lett 19:244–246 Shall S, Brightwell M, O'Farrell MK, Stone P, Whish WJD (1972) Properties of poly(ADP-ribose) polymerase in Physarum polycephalum and mouse fibroblasts. Hoppe-Seyler's Z Physiol Chem 353:846–847 Ueda K, Fukushima M, Okayama H, Hayaishi O (1975) Nicotinamide adenine dinucleotide glycohydrolase from rat liver nuclei. Isolation and characterization of a new enzyme. J Biol Chem 250:7541–7546 Claycomb WC (1976) Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle. Biochem J 154:387–393 Müller WEG, Zahn RK (1976) Poly ADP-ribosylation of DNA-dependent RNA polymerase I from quail oviduct. Dependence on progesterone stimulation. Mol Cell Biochem 12:147–159 Berger NA, Weber G, Kaichi AS (1978) Characterization and comparison of poly(adenosine diphosphoribose) synthesis and DNA synthesis in nucleotide-permeable cells. Biochim Biophys Acta 519:87–104 Levi V, Jacobson EL, Jacobson MK (1978) Inhibition of poly(ADP-ribose) polymerase by methylated xanthines and cytokinins. FEBS Lett 88:144–146 Terada M, Fujiki H, Marks PA, Sugimura T (1979) Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds. Proc Natl Acad Sci USA 76:6411–6414 Yamamoto H, Okamoto H (1980) Protection by picolinamide, a novel inhibitor of poly (ADP-ribose) synthetase, against both streptozotocin-induced depression of proinsulin synthesis and reduction of NAD content in pancreatic islets. Biochem Biophys Res Commun 95:474–481 Kitamura A, Tanigawa Y, Okamoto S, Miyake Y, Shimoyama M (1981) Theophylline reduces poly(ADP-ribose) synthetase from chick embryo liver nuclei. Biochim Biophys Acta 667:63–68 Kristensen T, Holtlund J (1978) Poly(ADP-ribose) polymerase from Ehrlich ascites tumor cells. Properties of the purified polymerase. Eur J Biochem 88:495–501 Banasik M, Ueda K (1999) Dual inhibitory effects of dimethyl sulfoxide on poly(ADP-ribose) synthetase. J Enzyme Inhib 14:239–250 Ueda K, Banasik M (1992) Inhibition of poly(ADP-ribose) synthetase activity by tryptophan metabolites. In: Ishiguro I, Kido R, Nagatsu T, Nagamura Y, Ohta Y (eds) Advances in tryptophan research 1992. Fujita Health University Press, Toyoake , pp 141–144 Virág L, Szabó C (2001) Purines inhibit poly(ADP-ribose) polymerase activation and modulate oxidant-induced cell death. FASEB J 15:99–107 Yoshihara K, Tanaka Y (1981) ADP-ribosylation of diadenosine 5', 5"'-P1, P4-tetraphosphate by poly(ADP-ribose) polymerase in vitro. J Biol Chem 256:6756–6761 Suzuki H, Tornese Buonamassa D, Weisz A (1990) Inverse relationship between poly (ADP-ribose) polymerase activity and 2',5'-oligoadenylates core level in estrogen-treated immature rat. Mol Cell Biochem 99:33–39 Tanaka T, Yamamoto D, Sato T, Tanaka S, Usui K, Manabe M, Aoki Y, Iwashima Y, Saito Y, Mino Y, Deguchi H (2011) Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity. J Nutr Sci Vitaminol (Tokyo) 57:192–196 Jackowski G, Kun E (1982) The influence of triiodothyronine on polyadenosine-diphosphoribose polymerase and RNA synthesis in cardiocyte nuclei. J Mol Cell Cardiol 14:65–70 Jackowski G, Kun E (1983) The effect of in vivo treatment with triiodothyronine on the in vitro synthesis of protein-poly(ADP)-ribose adducts by isolated cardiocyte nuclei and the separation of poly(ADP)-ribosylated proteins by phenol extraction and electrophoresis. J Biol Chem 258:12587–12593 Jackowski G, Kun E (1984) Evidence for the macromolecular basis of regulation of heart hypertrophy. Eur Heart J 5:219–224 Aranda A, Copp RP, Pascual A, Samuels HH (1991) Influence of thyroid hormone on ADP-ribosylation of nuclear proteins in cultured GH1 cells. FEBS Lett 279:179–183 Cesarone CF, Scarabelli L, Giannoni P, Orunesu M (1994) Hepatic poly(ADP-ribose) polymerase activity in rat is controlled by thyroid hormones. Biochem Biophys Res Commun 203:1548–1553 Giannoni P, Scarabelli L, Orunesu M, Cesarone CF (1995) In vitro effect of 3,5,3'-triiodothyronine on poly(ADP-ribosyl)ation of DNA topoisomerase I. Ital J Biochem 44:129–136 Tanuma S-i, Johnson LD, Johnson GS (1983) ADP-ribosylation of chromosomal proteins and mouse mammary tumor virus gene expression. Glucocorticoids rapidly decrease endogenous ADP-ribosylation of nonhistone high mobility group 14 and 17 proteins. J Biol Chem 258:15371–15375 Müller WEG, Totsuka A, Nusser I, Obermeier J, Rhode HJR, Zahn RK (1974) Poly(adenosine diphosphate-ribose) polymerase in quail oviduct. Changes during estrogen and progesterone induction. Nucleic Acids Res 1:1317–1327 Sun M, Zhao Y, Gu Y, Xu C (2011) Anti-inflammatory mechanism of taurine against ischemic stroke is related to down-regulation of PARP and NF-kB. Amino Acids. doi:10.1007/s00726-011-0885-3 Ha HC, Hester LD, Snyder SH (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 Kauppinen TM, Swanson RA (2005) Poly(ADP-ribose) polymerase-1 promotes microglial activation, proliferation, and matrix metalloproteinase-9-mediated neuron death. J Immunol 174:2288–2296 Yoshihara K (1972) Complete dependency of poly(ADP-ribose) synthesis on DNA and its inhibition by actinomycin D. Biochem Biophys Res Commun 47:119–125 Larsen AG, Østvold AC, Holtlund J, Kristensen T, Laland SG (1982) The inhibitory effect of Zn2+ on poly(ADP-ribose) polymerase activity and its reversal. Biochem J 203:511–513 Hartwig A, Asmuss M, Blessing H, Hoffmann S, Jahnke G, Khandelwal S, Pelzer A, Bürkle A (2002) Interference by toxic metal ions with zinc-dependent proteins involved in maintaining genomic stability. Food Chem Toxicol 40:1179–1184 Schwerdtle T, Hamann I, Jahnke G, Walter I, Richter C, Parsons JL, Dianov GL, Hartwig A (2007) Impact of copper on the induction and repair of oxidative DNA damage, poly(ADP-ribosyl)ation and PARP-1 activity. Mol Nutr Food Res 51:201–210 Yager JW, Wiencke JK (1997) Inhibition of poly(ADP-ribose) polymerase by arsenite. Mutat Res 386:345–351 Hartwig A, Pelzer A, Asmuss M, Bürkle A (2003) Very low concentrations of arsenite suppress poly(ADP-ribosyl)ation in mammalian cells. Int J Cancer 104:1–6 Walter I, Schwerdtle T, Thuy C, Parsons JL, Dianov GL, Hartwig A (2007) Impact of arsenite and its methylated metabolites on PARP-1 activity, PARP-1 gene expression and poly(ADP-ribosyl)ation in cultured human cells. DNA Repair (Amst) 6:61–70 Ding W, Liu W, Cooper KL, Qin X-J, de Souza Bergo PL, Hudson LG, Liu KJ (2009) Inhibition of poly(ADP-ribose) polymerase-1 by arsenite interferes with repair of oxidative DNA damage. J Biol Chem 284:6809–6817 Mendes F, Groessl M, Nazarov AA, Tsybin YO, Sava G, Santos I, Dyson PJ, Casini A (2011) Metal-based inhibition of poly(ADP-ribose) polymerase—the guardian angel of DNA. J Med Chem 54:2196–2206 Geraets L, Moonen HJJ, Wouters EFM, Bast A, Hageman GJ (2006) Caffeine metabolites are inhibitors of the nuclear enzyme poly(ADP-ribose)polymerase-1 at physiological concentrations. Biochem Pharmacol 72:902–910 Brightwell MD, Leech CE, O'Farrell MK, Whish WJD, Shall S (1975) Poly(adenosine diphosphate ribose) polymerase in Physarum polycephalum. Biochem J 147:119–129 Rickwood D, Osman MS (1979) Characterisation of poly(ADP-Rib) polymerase activity in nuclei from the slime mould Dictyostelium discoideum. Mol Cell Biochem 27:79–84 Benjamin RC, Gill DM (1980) Poly(ADP-ribose) synthesis in vitro programmed by damaged DNA. A comparison of DNA molecules containing different types of strand breaks. J Biol Chem 255:10502–10508 Banasik M, Komura H, Ueda K (1992) Specific inhibitors of poly(ADP-ribose) synthetase. In: Poirier GG, Moreau P (eds) ADP-ribosylation reactions. Springer-Verlag, New York, pp 343–350