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Enzymology of ADP-ribose polymer synthesis

Abstract

In this minireview, we summarize recent advances on the enzymology of ADP-ribose polymer synthesis. First, a short discussion of the primary structure and cloning of poly(ADP-ribose) polymerase (PARP) [EC 2.4.2.30], the enzyme that catalyzes, the synthesis of poly(ADP-ribose), is presented. A catalytic distinction between the multiple enzymatic activities of PARP is established. The direction of ADP-ribose chain growth as well as the molecular mechanism of the automodification reaction catalyzed by PARP are described. Current approaches to dissect ADP-ribose polymer synthesis into individual reactions of initiation, elongation and branching, as well as a partial mechanistic characterization of the ADP-ribose elongation reaction at he chemical level are also presented. Finally, recent developments in the catalytic characterization of PARP by site-directed mutagensis are also briefly summarized.

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References

  1. 1.

    Althaus F R, Richter C R.: ADP-ribosylation of Proteins. Mol Biol Biochem Biophys 37: 1–126 1987

  2. 2.

    Benjamin R C, Gill D M: Poly(ADP-ribose) Synthesisin vitro Programmed by Damaged DNA. A Comparison of DNA Molecules Containing Different Types of Strand Beaks. J Biol Chem 255: 10501–10508, 1980

  3. 3.

    Nishikimi N, Ogasawara K, Kameshita I Taniguchi T, Shizuta Y: Poly(ADP-ribose) Synthetase. The DNA Binding Domain and the Automodification Domain. J Biol Chem 257: 5102–6105, 1982

  4. 4.

    Kameshita I, Matsuda Z, Taniguchi T, Shizuta Y: Poly(ADP-ribose) Synthetase. Separation and Identification of the Three Proteolytic Fragments as the Substrate Binding Domain, the DNA-Binding Domain, and the Automodification Domain. J Biol Chem 259: 4770–4776, 1984

  5. 5.

    Kameshita I, Matzuda M, Nishikimi N, Ushiro H, Shizuta Y: Reconstitution and Poly(ADP-ribosyl)ation of Proteolytically Fragmented Poly(ADP-ribose) Synthetase. J Biol Chem 262: 3863–3868, 1986

  6. 6.

    Mazen A, Menessier-DeMurcia, J, Molinete M, Simonin F, Gradwohl G, Poirier G G, de Murcia G: Poly(ADP-ribose) Polymerase: A Novel Finger Protein. Nucl. Acids Res 17: 4689–4698, 1989

  7. 7.

    Menessier-DeMurcia J, Molinete M, Gradwohl G, Simonin F, DeMurcia G: Zinc Binding Domain of Poly(ADP-ribose) Polymerase Participates in the Recognition of Single Strand Breaks on DNA. J Mol Biol 210: 229–233, 1989

  8. 8.

    Ikejima M, Noiguchi S, Yamashita R, Ogura T, Sugimura T, Gill D M, 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. J Biol Chem 266: 21907–21913, 1991

  9. 9.

    Gradwohl G, Menessier de Murcia G, Molinete M, Simonin F, Koken M, Hoeijmakers J H J, deMurcia G: The Second Zinc Finges Domain of Poly(ADP-ribose) Polymerase Determines Specificity for Single-Stranded Breaks in DNA. Proc Natl Acad Sci USA 87: 2990–2994, 1990

  10. 10.

    Uchida K, Hanai S, Ishikawa K-I, Ozawa Y-I, Uchida M, Sugimura T, Miwa M: Cloning of cDNA encodingDrosophila Poly(ADP-ribose) Polymerase: Leucine Zipper in the Automodification Domain. Proc Natl Acad Sci USA 90: 3481–3484, 1993

  11. 11.

    Kurasaki T, Ushiro H, Mitsuchi Y, Suzuki S, Matsuda M, Matsuda Y, Katunuma N, Kangawa K Matsuo H, Hirose T, Inayama S, Shizuta Y: Primary Structure of Human Poly(ADP-ribose) Synthetase as Deduced from cDNA Sequence J Biol Chem 262: 15990–15997, 1987

  12. 12.

    Mendoza-Alvarez H, Alvarez-Gonzalez R: Poly(ADP-ribose) Polymerase is a Catalytic Dimer and the Automodification Reaction is intermolecular. J Biol Chem 268: 22575–22580, 1993

  13. 13.

    Huletsky A, Niedergang C, Frechette A, Aubin R, Gaudreau A, Poirier G G: Sequential ADP-ribosylation Pattern of Nucleosomal Histones. Eur J Biochem 146: 277–285, 1985

  14. 14.

    Boulikas T: At, Least 60 ADP-ribosylated Variant Histones are Present in Nuclei from Dimethylsulphate-treated and Untreated Cells. EMBO J 7: 57–67, 1988

  15. 15.

    Boulikas T: Poly(ADP-ribosylated) Histones in Chromatin Replication J Biol Chem 265: 14638–14647, 1990

  16. 16.

    Yoshihara K, Itaya A, Tanaka Y, Ohashi Y, Ito K, Teraoka H, Tsukuda K, Matsukage A, Kamiya T: Inhibition of DNA Polymerase α, DNA Polymerase, β, Terminal Deoxynucleotidyltransferase and DNA Ligase II by Poly(ADP-ribosyl)ation Reactionin vitro. Biochem Biophys Res Commun 128: 61–67, 1985

  17. 17.

    Ohahi Y: Effect of Ionic Strength on Chain Elongation in ADP-ribosylation of Various Nucleases. J Biochem 99: 971–979, 1986

  18. 18.

    Yoshihara K, Hashida T, Tanaka Y, Oghushi H: Enzyme-bound Early Product of Purified poly(ADP-ribose) Polymerase. Biochem Biophys Res Commun 78: 1281–1288, 1977

  19. 19.

    Kawaichi M, Ueda K, Hayaishi O: Multiple Auto-poly(ADP-ribosyl)ation of Rat Liver Poly(ADP-ribose) Synthetase: Mode of Modification, and Properties of Automodified Synthetase. J Biol Chem 256: 9483–9489, 1981

  20. 20.

    Adamietz P: Poly(ADP-ribose) Synthetase is the Major Endogenous Non-histone Acceptor for Poly(ADP-ribose) in Alkylated Rat Hepatoma Cells. Eur J Biochem 169: 365–372, 1987

  21. 21.

    Kreimeyer A, Wielckens K, Adamietz P, Hilz H: DNA-repair Associated ADP-ribosylationin vivo. Modification, of Histone H1 Differs from that of the Principal Acceptor Proteins. J Biol Chem 259: 890–896, 1984

  22. 22.

    Zahradka P, Ebisuzaki K: A Shuttle Mechanism for DNA-Protein Interations. The Regulation of Poly(ADP-ribose) Polymerase. Eur J Biochem 127: 579–585, 1982

  23. 23.

    Jump D B, Smulson M: Purification and Characterization of the Major Nonhistone Protein Acceptor for Poly(adenoisine diphosphate ribose) in He-La cell nuclei. Biochem 19: 1024–1030, 1980

  24. 24.

    Desmarais Y, Menard L, Lagueux J, Poirier G G: Enzymological Properties of Poly(ADP-ribose)polymerase. Characterization of Automodification Sites and NADase Activity. Biochem Biophys Acta 1087: 179–186, 1991

  25. 25.

    Ferro A M, Olivera B M: Poly(ADP-ribosylation)in vitro: Reaction parameters and Enzyme Mechanism J Biol Chem 257: 7808–7813 1982

  26. 26.

    Kawaichi M, Ueda K, and Hayaishi O: Initiation of Poly(ADP-ribosyl)-Histone Synthesis of Poly(ADP-ribose) Synthetase. J Biol Chem 255: 816–819, 1980

  27. 27.

    Miwa M, Saikawa N, Yamaizumi Z, Nishimura S, Sugimura T: Structure of Poly(adenosine diphosphate ribose): Identification of 2-(1″-ribosyl-2″-(or 3″-) (1″-ribosyl)adenosine-5″, 5″, 5″-tris(phosphate) as a Branch Linkage. Proc Natl Acad Sci USA 76: 595–599, 1979

  28. 28.

    Naegeli H, Loetscher P, Althaus F R: Poly ADP-ribosylation of Proteins: Processivity of Post-translational Modification. J Biol Chem 264: 14382–14384, 1989

  29. 29.

    Ueda K, Kawaichi M, Okayama H, Hayaishi O: Poly(ADP-ribosyl)ation of Nuclear Proteins: Enzymatic Elongation of Chemically Synthesized ADP-ribose Histone Adducts. J Biol Chem 254: 679–687, 1979

  30. 30.

    Taniguchi T: Reaction Mechanism for Automodification of Poly(ADP-ribose) Synthetase. Biochem Biophys Res Commun 147: 1008–1012, 1987

  31. 31.

    Alvarez-Gonzalez R: L 3′-deoxy-NAD+ as a Substrate for Poly(ADP-ribose) Polymerase and the Reaction Mechanism of Poly(ADP-ribose) Elongation. J Biol Chem 263: 17690–17696, 1988

  32. 32.

    Bauer P I, Buki K G, Hakam A, Kun E: Macromolecular Association of ADP-ribosyltransferase and its Correlation with Enzymic Activity. Biochem J 270: 17–26, 1990

  33. 33.

    Butt T R, Smulson M: Relationship Between Nicotinamide Adenine Dinucleotide and in Vitro Synthesis of Poly(adenosine Diphosphate ribose) on Purified Nucleosomes. Biochem 19: 5235–5242, 1980

  34. 34.

    Tanigawa Y, Tsuchiya M, Imai Y, Shimoyama M: ADP-ribo-syltransferase from Hen Liver Nuclei. J Biol Chem 259: 2022–2029, 1984

  35. 35.

    Wielckens K, Schimidt A, George E, Bredehorst R, Hilz H: DNA Fragmentation and NAD Depletion: Their Relation to the Turnover of Endogenous Mono(ADP-ribosyl) and Poly(ADP-ribosyl) Proteins. J Biol Chem 257: 12872–12877, 1982

  36. 36.

    Jacobson E L, Antoe K M, Juarez-Salinas H, Jacobson M K: Poly(ADP-ribose) Metabolism in Ultraviolet Irradiated Human Fibroblasts. J Biol Chem 258: 103–107, 1983

  37. 37.

    Alvarez-Gonzalez R, Althaus F R: Poly(ADP-ribose) Catabolism in mammalian Cells Exposed to DNA-damaging Agents. Mutation Res 218: 67–74, 1989

  38. 38.

    Loetscher P, Alvarez-Gonzalez R, Althaus F R: Poly(ADP-ribose) May Signal Changing Metabolic conditions to the Chromatin of Mammalian Cells. Proc Natl Acad Sci USA 84: 1286–1289, 1987

  39. 39.

    Alvarez-Gonzalez R, Jacobson M K: Characterization of Polymers of Adenosine Diphosphate Ribose Generatedin vitro andin vivo. Biochemistry 26: 3218–3224, 1987

  40. 40.

    Kiehlbauch C C, Aboul-Ela N, Jacobson E L, Ringer S P, Jacobson M: High Resolution Fractionation and Characterization of ADP-ribose Polymers. Anal. Biochem 208: 26–34, 1993

  41. 41.

    Alvarez-Gonzalez R: Synthesis and Purification of Deoxyribose Analogues of NAD+ by Affinity Chromatography and SAX-HPLC. J Chromatography 444: 89–85, 1988

  42. 42.

    Alvarez-Gonzalez R, Panzeter P, Ringer D P, Mendoza-Alvarez H O: Poly(3′-dADP-ribosyl)ation of Proteins in Liver Chromatic Isolated from Rats Fed with Hepatocarcinogens. In: Poirier, G.G. and Moreau, P., eds, ADP-ribosylation Reactions, Springer-Verlag, New York, Berlin-Heidelberg, pp 149–252, 1992

  43. 43.

    Pacheco-Rodriguez G, Moss J, Alvarez-Gonzalez R: ADP-ribose Elongation of Mono-(ADP-ribosyl)-arginine Methyl Ester by Poly(ADP-ribose) Polymerase. FASEB Journal 7: A1196, 1993

  44. 44.

    Alvarez-Gonzalez R, Moss J, Niedergang C Althaus F R: Selective probing of ADP-ribosylation reactions with Oxidized 2-Deoxy-nicotinamide Adenine Dinucleotide. Biochemistry 27: 5378–5383, 1988

  45. 45.

    Simonin F, Menesseier-de Murcia J, Poch O, Muller S, Gradwohl G, Molinete M, Penning C Keith G, de Murcia G: Expression and Site Directed Mutagenesis of The Catalytic Domain of Human Poly(ADP-ribose) Polymerase inEcherichia coli. J Biol Chem 265: 19249–19256, 1990

  46. 46.

    Simonin F, Poch O, Delarue M, de Murcia G: Identification of Potential Active-site Residues in the Human Poly(ADP-ribose) Polymerase. J Biol Chem 268: 852908535, 1993

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Correspondence to Rafael Alvarez-Gonzalez.

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Alvarez-Gonzalez, R., Pacheco-Rodriguez, G. & Mendoza-Alvarez, H. Enzymology of ADP-ribose polymer synthesis. Mol Cell Biochem 138, 33–37 (1994). https://doi.org/10.1007/BF00928440

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Key words

  • poly(ADP-ribose) polymerase
  • structure
  • chemistry
  • kinetics
  • automodification
  • mechanism(s)