ADP-Ribosylation of Proteins: A Ubiquitous Cellular Control Mechanism

  • Sydney Shall
Part of the Advances in Experimental Medicine and Biology book series (NATO ASI F, volume 231)


ADP-ribosylation reactions are ubiquitous; the enzymes catalyse the transfer of the ADP-ribose portion of NAD to proteins. These reactions seem to regulate a wide variety of cellular functions. ADP-ribosyl transferase (ADPRT) enzymes occur in both the nucleus and the cytoplasm. The nuclear ADPRT synthesises homopolymers of ADP-ribose on suitable acceptor proteins; the polymers may be linear or branched. The nuclear enzyme is confined to nucleated cells, but is found in nucleated protozoa, plants and animals. The cytoplasmic enzymes seem to be able to catalyse only the formation of mono-ADP-ribosyl protein products. These mono-ADPRT enzymes are ubiquitous and occur in bacteria, bacteriophages, protozoa, plants, animals and viruses. The physiological functions of the nuclear enzyme has been shown to include the regulation of DNA repair. It probably also regulates the conformation of chromatin. Nuclear poly(ADP-ribose) consists of a constitutive fraction with a half-life of about 8 hours and an activated fraction, which is produced in response to DNA damage and the consequent DNA strand-breaks; the activated fraction has a very short half-life, possibly less than one minute. The nuclear enzyme may also be involved in certain cases of cell differentiation, in antigenic variation in trypanosomes, in DNA transfection and possibly in malignant transformation.


Sister Chromatid Exchange Nicotinamide Adenine Dinucleotide Repair Synthesis Mouse Leukaemia Cell Nicotinamide Mononucleotide 
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  1. Althaus, F. R., Lawrence, S. D., Sattler, G. L. and Pitot, H. C., 1982, ADP-Ribosyltansferase activity in cultured hepatocytes, J. Biol. Chem., 257:5535.Google Scholar
  2. Althaus, F. R., Hilz, H. and Shall, S., 1985, “ADP-Ribosylation of proteins,” Springer Verlag, Berlin.CrossRefGoogle Scholar
  3. Berger, N. A. and Sikorski, G. W., 1980, Nicotinamide stimulates repair of DNA damage in human lymphocytes, Biochem. Biophys. Res. Commun., 95:67.PubMedCrossRefGoogle Scholar
  4. Brightwell, M. D., Leech, C. E., O’Farrell, M. K., Whish, W. J. D. and Shall, S., 1975, Poly(ADP-Ribose) polymerase in Physarum polycephalum, Biochem. J., 147:119.PubMedGoogle Scholar
  5. Cornelissen, A. W. C. A., Michels, P. A. M., Borst, P., Spanjer, W., Versluijs-Broers, J. A. M., Van der Meer, C., Farzaneh, F. and Shall, S., 1985, Effect of 3-aminobenzamide on antigenic variation of Trypanosoma brucei, Biochem. Pharmacol., 34:4151.PubMedCrossRefGoogle Scholar
  6. Creissen, D. and Shall, S., 1982, Regulation of DNA ligase activity by poly(ADP-Ribose), Nature (Lond.), 296:271.CrossRefGoogle Scholar
  7. Davies, M. I., Halldorsson, H., Shall, S. and Skidmore, C. J., 1976, The action of streptozotocin on mouse leukaemia cells, Biochem. Soc. Trans., 4:635.PubMedGoogle Scholar
  8. Davies, M. I., Shall, S. and Skidmore, C. J., 1977, Poly(ADP-Ribose) polymerase and DNA damage, Biochem. Soc. Trans., 5:949.PubMedGoogle Scholar
  9. Davies, M. I., Halldorsson, H., Nduka, N., Shall, S. and Skidmore, C. J., 1978, The involvement of poly(ADP-Ribose) in DNA repair, Biochem. Soc. Trans., 6:1056.PubMedGoogle Scholar
  10. Durkacz, B. W., Omidiji, O., Gray, D. A. and Shall, S., 1980, (ADP-Ribose) participates in DNA excision repair, Nature, (Lond.), 283:593.CrossRefGoogle Scholar
  11. Durkacz, B. W., Irwin, J. and Shall, S., 1981, Inhibition of (ADP-Ribose) biosynthesis retards DNA repair but does not inhibit repair synthesis, Biochem. Biophys. Res. Commun., 101:1433.PubMedCrossRefGoogle Scholar
  12. Farzaneh, F., Shall, S. and Zalin, R., 1980, DNA strand-breaks and poly (ADP-ribose) polymerase activity during chick muscle differentiation, in: “Novel ADP-Ribosylations of regulatory enzymes and proteins,” M. Smulson and T. Sugimura, eds., Elsevier, Amsterdam.Google Scholar
  13. Farzaneh, F., Zalin, R. and Shall, S., 1984, Single-strand DNA breaks are formed during muscle cell differentiation, Exp. Biol. Med., 9:260.Google Scholar
  14. Farzaneh, F., Zalin, R., Brill, D. and Shall, S., 1982, DNA strand-breaks and ADP-Ribosyl activation during cell differentiation, Nature,(Lond.), 300:362.CrossRefGoogle Scholar
  15. Farzaneh, F., Shall, S. and Johnstone, A. P., 1985, The dynamic nature of DNA strand-breaks present in differentiating muscle cells and quiescent lymphocytes. FEBS Letters, 189:62.PubMedCrossRefGoogle Scholar
  16. Farzaneh, F., Shall, S., Michels, P. and Borst, P., 1985, ADP-Ribosyl transferase activity in Trypanosoma brucei, Molec. Biochem. Parasitol., 14:251.CrossRefGoogle Scholar
  17. Farzaneh, F., Lebby, R. A., Brill, D. A., Meldrum, R., Feon, S., David, J-C. and Shall, S., 1987, DNA repair in human promyelocytic leukaemia cell line, HL 60, Nucl. Acids Res., 15:3503.PubMedCrossRefGoogle Scholar
  18. Goodwin, P. M., Lewis, P. J., Davies, M. I., Skidmore, C. J. and Shall, S., 1978, The effect of gamma-irradiation and neocarzinostatin on NAD and ATP levels in mouse leukaemia cells, Biochem. Biophys. Acta, 543:576.PubMedCrossRefGoogle Scholar
  19. Gray, D. A., Durkacz, B. W. and Shall, S., 1981, Inhibitors of nuclear ADP-Ribosyl transferase retard DNA repair after N-methyl-N-nitroso-urea, FEBS Letters, 131:173.PubMedCrossRefGoogle Scholar
  20. Halldorsson, H., Gray, D. A. and Shall, S., 1978, Poly(ADP-Ribose) polymerase activity in nucleotide permeable cells, FEBS Letters, 85:349.PubMedCrossRefGoogle Scholar
  21. Jacobson, E. L., Lange, R. A. and Jacobson, M.K., 1979, Pyridine nucleotide synthesis in 3T3 cells. J. Cell. Physiol., 99:417.PubMedCrossRefGoogle Scholar
  22. James, M. R. and Lehmann, A. R., 1982, Role of poly(APD-Ribose) in DNA repair in human fibroblasts, Biochemistry, 21:4007.PubMedCrossRefGoogle Scholar
  23. Miwa, M., Kanai, M., Kondo, T., Hoshino, H., Ishihara, K. and Sugimura, T., 1981, Inhibitors of poly(ADP-Ribose) polymerase enhance unscheduled DNA sysnthesis in human peripheral lymphocytes. Biochem. Biophys. Res. Commun., 100:463.PubMedCrossRefGoogle Scholar
  24. Nduka, N., Skidmore, C. J. and Shall, S., 1980, The enhancement of cytotoxicity of N-methyl-N-nitroso-urea and of gamma-irradiation by inhibitors of poly(ADP-Ribose) polymerase, Eur. J. Biochem., 105:525.PubMedCrossRefGoogle Scholar
  25. Ohashi, Y., Ueda, K., Kawaichi, M. and Hayaishi, O., 1983, Activation of DNA ligase by poly(ADP-Ribose) in chromatin, Proc. Natl. Acad. Sci. USA., 80:3604.PubMedCrossRefGoogle Scholar
  26. Oikawa, A., Tohda, H., Kanai, M., Miwa, M. and Sugimura, T., 1980, Inhibitors of poly(ADP-ribose) polymerase induce sister chromatid exchanges, Biochem Biophys. Res. Commun., 97:1311.PubMedCrossRefGoogle Scholar
  27. Purnell, M. R. and Whish, W. J. D., 1980, Novel inhibitors of poly(ADP-Ribose) synthetase, Biochem. J., 185:775.PubMedGoogle Scholar
  28. Shall, S., 1975, Experimental manipulation of the specific activity of poly(ADP-Ribose) polymerase, J. Biochem. Tokyo, 77:2p.PubMedGoogle Scholar
  29. Shall, S., 1984a, ADP-Ribose in DNA repair: A new component of DNA excision repair, Adv. Rad. Biol., 11:1.Google Scholar
  30. Shall, S., 1984b, Inhibition of DNA repair by inhibitors of nuclear ADP-Ribosyl transferase, Nucl. Acids Res. Symposium Series, 13:143.Google Scholar
  31. Shall, S., 1985, ADP-Ribosylation as a cellular control mechanism, in: “ADP-Ribosylation of proteins,” F. R. Althaus, H. Hilz, S. Shall, eds. Springer Verlag, Berlin, pp 9–29.CrossRefGoogle Scholar
  32. Shall, S., O’Farrell, M. K., Stone, P. R. and Whish, W. J. D., 1974, Properties of the chromosomal enzyme, poly(ADP-Ribose) polymerase in cell growth and replication in normal and cancer cells, in: Differentiation and control of malignancy of tumor cells, W. Nakahara, T. Ono, T. Sugimura and H. Sugano, eds., Univ. of Tokyo Press, Tokyo, pp.69–85.Google Scholar
  33. Sims, J. L., Sikorski, G. W., Catino, D. M., Berger, S. J. and Berger, N. A., 1982, Poly(ADP-ribose) polymerase inhibitors stimulate unscheduled DNA synthesis in normal human lymphocytes, Biochemistry., 21:1813.PubMedCrossRefGoogle Scholar
  34. Skidmore, C. J., Davies, M. I., Goodwin, P. M., Halldorsson, H., Lewis, P. J., Shall, S. and Zia’ee, A., 1979, The invovlement of poly(ADP-Ribose) polymerase in the degradation of NAD caused by gamma-radiation and N-methyl-N-nitroso-urea, Eur. J. Biochem., 101:135.PubMedCrossRefGoogle Scholar
  35. Tsopanakis, C., Leer, J. C., Shall, S. and Westergaard, O., 1978a, Presence of poly(ADP-Ribose) metabolizing enzymes in Tetrahymena pyriformis, FEBS Letters, 93:207.CrossRefGoogle Scholar
  36. Tsopanakis, C., Leeson, E., Tsopanakis, A. and Shall, S., 1978b, Purification and properties of poly(ADP-Ribose) polymerase from pig thymus nuclei, Eur. J. Biochem., 90:337.CrossRefGoogle Scholar
  37. Ueda, K. and Hayaishi, O., 1985, ADP-Ribosylation, Ann. Rev. Biochem., 54:73PubMedCrossRefGoogle Scholar
  38. Utakoji, T., Hosoda, K., Umezawa, K., Sawamura, M., Matsushima, M., Miwa, M. and Sugimura, T., 1979, Induction of sister chromatid exchanges by nicotinamide in Chinese hamster lung fibroblasts and human lymphoblastoid cells, Biochem. Biophys. Res. Commun., 90:1147.PubMedCrossRefGoogle Scholar
  39. Whish, W. J. D., Davies, M. I. and Shall, S., 1975, Stimulation of poly(ADP-Ribose) polymerase activity by the anti-tumour antibiotic, streptozotocin, Biochem. Biophys. Res. Commun., 65:722.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Sydney Shall
    • 1
  1. 1.Cell and Molecular Biology LaboratoryUniverity of SussexBrightonEngland

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