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Poly(ADP-ribose) catabolism in mammalian cells


Poly(ADP-ribose) catabolism is a complex situation involving many proteins and DNA. We have developed anin vitro turnover system where poly(ADP-ribose) metabolism is monitored in presence of different relative amounts of two principal enzymes poly(ADP-ribose) transferase and poly(ADP-ribose) glycohydrolase along with other proteins and DNA. Our current results reviewed here show that the quality of polymer, i.e. chain length and complexity, as well as preference for the nuclear substrate varies depending upon the availability of poly(ADP-ribose) glycohydrolase. These results are interpreted in the light of the recent data implicating poly(ADP-ribose) metabolism in DNA-repair. (Mol Cell Biochem 138: 45–52 1994)

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  1. 1.

    de Murcia G, Huletsky A, Lamarre D, Gaudreau A, Pouyet J, Daune M, Poirier GG: Modulation of chromatin superstructure induced by poly(ADP-ribose) synthesis and degradation. J Biol Chem 261:7011–7017, 1986

  2. 2.

    Thibault, L, Hengartner, M, Lagueux J, Poirier, GG, Muller, S: Rearrangements of the nucleosome structure in chromatin by poly(ADP-ribose). Biochim Biophys Acta 1121:317–324, 1992

  3. 3.

    Satoh MS, Lindahl T: role of Poly(ADP-ribose) Formation in DNA Repair. Nature 356:356–358, 1992

  4. 4.

    Satoh MS, Poirier GG, Lindahl T: DNA+-Dependent Repair of Damaged DNA by Human Cell Extracts. J Biol Chem 268:5480–5487, 1993

  5. 5.

    Molinete M, Vermeulen W, Bürkle A, Ménissier-de Murcia J, Küpper JH, Hoeijmakers, JHJ, de Murcia G: Overproduction of poly(ADP-ribose) polymerase DNA-binding domain blocks alkylation-induced DNA repair synthesis inmammalian cells. Embo J 12:2109–2117, 1993

  6. 6.

    Althaus FR, Richter C: ADP-ribosylation of proteins. Enzymology and biological significance. Mol Biol Biochem Biophys 37:1–237, 1987

  7. 7.

    Cleaver JE, Morgan WF: poly(ADP-ribose)polymerase: a perplexing participant in cellular responses to DNA breakage. Mutat Res 257:1–18, 1991

  8. 8.

    Ghani QP, Hussain MZ, Zhang J, Hunt KH: Control of procollagen gene transcription and prolyl hydroxylase activity by poly(ADP-ribose) In: GG Poirier and P Moreau (eds) ADP-Ribosylation Reactions, Springer-Verlag, New-York, 1992, pp 211–217

  9. 9.

    Althaus FR, Lawrence SD, Sattler GL, Longfellow DG, Pitot HC: Chemical quantification of unscheduled DNA synthesis in culture hepatocytes as an assay for the rapid screening of potential chemical carcinogens. Cancer Research 42:3010–3015, 1982

  10. 10.

    Caplan AI, Rosenberg MJ: Interrelationship between poly(ADP-ribose) synthesis, intracellular NAD levels, and muscle or cartilage differentiation from mesodermal cells of embryonic chick limb. Proc Natl Acad Sci USA 72:1852–1857, 1975

  11. 11.

    Farzaneh F, Zalin R, Brill D, Shall SD: DNA strand breaks and ADP-ribosyl transferase activation during cell differentiation. Nature 300:362–366, 1982

  12. 12.

    McNerney R, Tavasolli M, Shall S, Brazinski A, Johnstone A: Changes in mRNA levels of poly(ADP-ribose) polymerase during activation of human lymphocytes. Biochem Biophys Acta 1009:185–187, 1989

  13. 13.

    Niedergang C, De Murcia G, Ittel ME, Pouyet J, Mandel P: Time course of polynucleosome relaxation and ADP-ribosylation. Correlation between relaxation and histone H1 hyper-ADP-ribosylation. Eur J Biochem 146: 185–191, 1985

  14. 14.

    Boulikas T: At least 60 ADP-ribosylated variant histones are present in nuclei from dimethylsulfate-treated and untreated cells. EMBO J 7: 57–67, 1988

  15. 15.

    Panzeter PL, Realini CA, Althaus FR: Noncovalent Interactions of Poly(adenosinc Diphosphate Ribose) with Histones. Biochemistry 31: 1379–1385, 1992

  16. 16.

    Grübe K, Bürkle A: Poly(ADP-ribose) Polymerase Activity in Mononuclear Leukocytes of 13 Mammalian Species Correlates with Species-Specific Life Span. Proc Natl Acad Sci USA 89:11759–11763, 1992

  17. 17.

    Pero RW, Holmgren K, Persson L: γ-radiation induced ADP-ribosyl transferase activity and mammalian longevity. Mutation Res 142:69–73, 1985

  18. 18.

    Kreimeyer A, Wielckens K, Adamietz P, Hilz H: DNA-repair-assocciated ADP-ribosylationin vivo. J Biol Chem 259:890–896, 1984

  19. 19.

    Sugimura T, Masutani M, Ogura T, Takenouchi N, Ikejima M, Esumi H: Regulation of DNA polymerase β by Poly(ADP-ribose) polymerase. In: GG Poirier and P Moreau (eds). ADP-Ribosylation Reactions. Springer-Verlag, New-York, 1992, pp 276–281

  20. 20.

    Ménissier-de Murcia J, Molinete M, Gradwohl G, Simonin F, de Murcia G: Zinc-binding domain of poly(ADP-ribose)polymerase participates in the recognition of single strand breaks on DNA. J Mo. Biol 210: 229–233, 1989

  21. 21.

    Ikejima M, Noguchi S, Yamashita R, Ogura T, Sugimura T, Gill DM, Miwa M: The zinc fingers of human poly(ADP-ribose) polymerase are differentially required for the recognition of DNA breaks and nicks and the consequent enzyme activation. Other structures recognize intact DNA. J Biol Chem 265:21907–21913, 1990

  22. 22.

    Ménard L, Thibault L, Poirier GG: Reconstitution of an in vitro poly(ADP-ribose) turnover system. Biochim Biophys Acta 1049:45–58, 1990

  23. 23.

    Benjamin RC, Gill DM: 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, 1980

  24. 24.

    Ohgushi H, Yoshihara K, Kamiya T: Bovine thymus poly(adenosine diphosphate ribose) polymerase physical properties and binding to DNA. J Biol Chem 255:6205–6211, 1980

  25. 25.

    Herzog H, Zabel BU, Schneider R, Auer B, Hirsch-Kauffmann M, Schweiger M: Human nuclear NAD+ ADP-ribosyltransferase: localization ofthe gene on chromosome 1q41-q42 and expression of an active human enzyme in Escherichia coli. Proc Natl Acad Sci USA 86:3514–3518, 1989

  26. 26.

    Hatakeyama K, Nemoto Y, Ueda K, Hayaishi O: Purification and characterization of poly(ADP-ribose) glycohydrolase. Different modes of action on large and small poly(ADP-ribose) J Biol Chem 261:14902–14911, 1986

  27. 27.

    Yamanaka H, Penning CA, Willis EH, Wasson DB, Carson DA: Characterization of human poly(ADP-ribose) polymerase with autoantibodies. J Biol Chem 263:3879–3883, 1988

  28. 28.

    Lamarre D, Talbot B, de Murcia G, Laplante C, Leduc Y, Mazen A, Poirier GG: Structural and functional analysis of poly(ADP-ribos) polymerase: an immunological study. Biochim Biophys Acta 950:147–160, 1988

  29. 29.

    Kaufmann SH, Brunet G, Talbot B, Lamarre D, Dumas C, Shaper JH, Poirier GG: Association of poly(ADP-ribose) polymerase with the nuclear matrix: the role of intermolecular disulfide bond formation, RNA retention, and cell type. Exp Cell Res 192:524–535, 1991

  30. 30.

    Tanuma S, Kawashima K, Endo H: Acceptor proteins for (ADP-ribose)n in the HeLa S3 cell cycle. J Biochem (Tokyo) 99:915–922, 1986

  31. 31.

    Bhatia K, Pommier Y, Giri C, Fornace AJ, Imaizumi M, Breitman TR, Cherney BW, Smulson ME: Expression of the poly(ADP-ribose) polymerase gene following natural and induced DNA strand breakage and effect of hyperexpression on DNA repair. Carcinogenesis 11:123–128, 1990

  32. 32.

    Alvarez-Gonzalez R, Althaus FR: Poly(ADP-ribose) catabolism in mammalian cells exposed to DNA-damaging agents. Mutation Res 218:67–74, 1989

  33. 33.

    Jonsson GG, Jacobson EL, Jacobson MK: Mechanism of alteration of poly(adenosine diphosphate-ribose) metabolism by hyperthermia. Cancer Res 48:4233–4239, 1988

  34. 34.

    Jonsson GG, Ménard L, Jacobson EL, Poirier GG, Jacobson MK: Effect of hyperthermia on poly(adenosine diphosphate-ribose) glycohydrolase. Cancer Res 48:4240–4243, 1988

  35. 35.

    Banasik M, Komura H, Shimoyama M, Ueda K: Specific Inhibitors of Poly(ADP-Ribose) Synthetase and Mono(ADP-ribosyl transferase. J Biol Chem 267:1569–1575, 1992

  36. 36.

    Ueda K, Oka J, Narumiya S, Miyakawa N, Hayaishi O: Poly ADPribose glycohydrolase from rat liver nuclei, a novel enzyme degrading the polymer. Biochem Biophys Res Commun 46:516–523, 1972

  37. 37.

    Zahradka P, Ebisuzaki K: A shuttle mechanism for DNA-protein interactions. The regulation of poly ADPr polymerase. Eur J Biochem 127:579–585, 1982

  38. 38.

    Shall S: ADPR in DNA repair: a new component of DNA excision repain. Adv Rad Biol 11:1–69, 1984

  39. 39.

    Wielckens K, George E, Pless T, Hilz H: Stimulation of poly (ADPribosyl)ation during Ehrlich ascites tumor cell ‘starvation’ and suppression of concomitant DNA fragmentation by benzamide. J Biol Chem 258:4098–4104, 1983

  40. 40.

    Juarez-Salinas H, Sims JL, Jacobson MK: Poly (ADP-ribose) levels in carcinogen-treated cells. Nature 282:740–741, 1979

  41. 41.

    Desmarais Y, Ménard L, Lagueux J, Poirier GG: Enzymological properties of poly(ADP-ribose) polymerase: characterization of automodification sites and NADase activity. Biochim Biophys Acta 1078:179–186, 1991

  42. 42.

    Bauer PI, Buki KG, Hakam A, Kun E: Macromolecular association of ADP-ribosyltransferase and its correlation with enzymic activity. Biochem J 270:17–26, 1990

  43. 43.

    Thomassin H, Ménard L, Hengartner C, Kirkland JB, Potner GG: Poly(ADP-ribosyl)ation of chromatin in an in-vitro poly(ADP-ribose)-turnover system. Biochim Biophys Acta 1137:171–181, 1992

  44. 44.

    Hengartner C, Lagueux J, Poirier GG: Analysis of the Activation of Poly(ADP-Ribose) Polymerase by Various Types of DNA. Biochemistry and Cell Biology 69:577–580, 1991

  45. 45.

    Ménard L, Poirier GG: Rapid assay of poly(ADP-ribose) glycohydrolase. Biochem Cell Biol 65:668–673, 1987

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Correspondence to Guy G. Poirier.

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Lagueux, J., Shah, G.M., Ménard, L. et al. Poly(ADP-ribose) catabolism in mammalian cells. Mol Cell Biochem 138, 45–52 (1994).

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Key words

  • poly (ADP-ribose) metabolism
  • turnover
  • chromatin
  • DNA-repair
  • histones