Abstract
Nuclear ADP-ribosyl transferase (ADPRT)1,2 catalyses the transfer of ADP-ribose from NAD+ to chromatin proteins to form mono-, oligo- and poly (ADP-ribose)-modified chromatin proteins3–7. The enzyme is entirely dependent on DNA for activity8 and is activated by nicks in the DNA9–11. Both radiation and alkylating agents deplete cells of NAD which is used to make (ADP-ribose)n (refs 1, 2, 12, 15–17), and this depletion is prevented by inhibitors of ADPRT13,15,18–25. ADPRT inhibitors also retard DNA strand-rejoining after damage1,2,26,27, and potentiate the lethality of DNA-damaging agents1,2,28. N-methyl-N′-nitro-N-nitrosoguanidine, an alkylating agent, transiently increases intracellular (ADP-ribose)n over 100-fold17. These data suggest that (ADP-ribose)n biosynthesis is necessary for effective repair of some types of DNA damage1. The question remains of which step in DNA repair requires ADPRT activity. The enzyme inhibitors do not prevent incision events1,2,27 nor do they inhibit repair replication29–31. Here we describe experiments which support the hypothesis that ADP-ribosylation activates DNA ligase activity. We suggest that ADPRT has a general function in the control of the breaking and rejoining of DNA.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Durkacz, B. W., Omidiji, O., Gray, D. A. & Shall, S. Nature 283, 593–596 (1980).
Durkacz, B. W., Nduka, N., Omidiji, O., Shall, S. & Zia'ee, A-A. in Novel ADP-ribosylations of Regulatory Enzymes and Proteins (eds Smulson, M. E. & Sugimura, T.) 207–216 (Elsevier, Amsterdam, 1980).
Sugimura, T. Prog. Nucleic Acid Res. molec. Biol. 13, 127–151 (1973).
Hilz, H. & Stone, P. R. Rev. Physiol. Biochem. Pharmac. 76, 1–58 (1976).
Hayaishi, O. & Ueda, K. A. Rev. Biochem. 46, 95–116 (1977).
Purnell, M. R., Stone, P. R. & Whish, W. J. D. Biochem. Soc. Trans. 8, 215–227 (1980).
Smulson, M. E. & Sugimura, T. (eds) Novel ADP-ribosylations of Regulatory Enzymes and Proteins (Elsevier, Amsterdam, 1980).
Tsopanakis, C., Leeson, E., Tsopanakis, A. & Shall, S. Eur. J. Biochem. 90, 337–345 (1978).
Halldorsson, H., Gray, D. A. & Shall, S. FEBS Lett. 85, 349–352 (1978).
Berger, N. A., Weber, G. & Kaichi, A. S. Biochim. biophys. Acta 519, 87–104 (1978).
Benjamin, R. & Gill, M. J. biol. Chem. 255, 10493–10508 (1980).
Whish, W. J. D., Davies, M. I. & Shall, S. Biochem. biophys. Res. Commun. 65, 722–730 (1975).
Davies, M. I., Shall, S. & Skidmore, C. J. Biochem. Soc. Trans. 5, 949–950 (1978).
Davies, M. I., Halldorsson, H., Nduka, N., Shall, S. & Skidmore, C. J. Biochem. Soc. Trans. 6, 1056–1057 (1978).
Skidmore, C. J. et al. Eur. J. Biochem. 101, 135–142 (1979).
Jacobson, M. K., Levi, V., Juarez-Salinas, H., Barton, R. A. & Jacobson, E. L. Cancer Res. 40, 1797–1802 (1980).
Juarez-Salinas, H., Sims, J. L. & Jacobson, M. K. Nature 282, 740–741 (1979).
Preiss, J., Schlaeger, R. & Hilz, H. FEBS Lett. 19, 244–246 (1971).
Clark, J. B., Ferris, G. M. & Pinder, S. Biochim. biophys. Acta 238, 82–85 (1971).
Shall, S. et al. Biochem. Soc. Symp. 42, 103–116 (1977).
Claycomb, W. C. Biochem. J. 154, 387–393 (1976).
Levi, V., Jacobson, E. L. & Jacobson, M. K. FEBS Lett. 8, 144–146 (1978).
Khan, M. G. thesis, Univ. Sussex (1977).
Shall, S. J. Biochem., Tokyo 77, 2p (1975).
Purnell, M. R. & Whish, W. J. D. Biochem. J. 185, 775–777 (1980).
Durkacz, B. W., Irwin, J. & Shall, S. Eur. J. Biochem. 121, 65–69 (1981).
Gray, D. A., Durkacz, B. W. & Shall, S. FEBS Lett. 131, 173–177 (1981).
Nduka, N., Skidmore, C. J. & Shall, S. Eur. J. Biochem. 105, 525–530 (1980).
Durkacz, B. W., Irwin, J. & Shall, S. Biochem. biophys. Res. Commun. 101, 1433–1441 (1981).
James, M. R. & Lehmann, A. R. in DNA Repair, Chromosome Alterations and Chromatin Structure (eds Natarajan, A. T., Altman, H. & Obe, G.) (Elsevier, Amersterdam, in the press).
Miwa, M. et al. Biochem. biophys. Res. Commun. 100, 463–470 (1981).
Söderhall, S. & Lindahl, T. Biochem. biophys. Res. Commun. 53, 910–916 (1973).
Söderhall, S. & Lindahl, T. J. biol. Chem. 250, 8438–8444 (1975).
Teraoka, H., Shimoyachi, M. & Tsukada, K. FEBS Lett. 54, 217–220 (1975).
Evans, D. G., Ton, S. H. & Keir, H. M. Biochem. Soc. Trans. 3, 1131–1132 (1975).
Zimmerman, S. B. & Levin, C. J. J. biol. Chem. 250, 149–155 (1975).
Söderhall, S. Nature 260, 640–642 (1976).
Söderhall, S. & Lindahl, T. FEBS Lett. 67, 1–8 (1976).
Teraoka, H., Shimoyachi, M. & Tsukada, K. J. Biochem. 81, 1253–1260 (1977).
Inone, N. & Kato, T. Proc. Japan Acad. 52, 461–464 (1976).
Nakaya, N., Sawasaki, Y., Teraoka, M., Nakajima, H. & Tsukada, K. J. Biochem. 81, 1575–1577 (1977).
Mezzina, M. & Nocentini, S. Nucleic Acids Res. 5, 4317–4328 (1978).
David, J. C., Vinson, D., Letresne, J. & Signoret, J. J. Cell Differentiation 8, 451–459 (1979).
David, J. C., Vinson, D. & Fedecka Bruner, B. Expl Cell Res. 130, 137–146 (1980).
Weiss, B., Live, T. R. & Richardson, C. C. J. biol. Chem. 243, 4530–4542 (1968).
Weiss, B., Jacquemin-Sablon, A., Live, T. R., Farced, G. C. & Richardson, C. C. J. biol. Chem. 243, 4543–4555 (1968).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Creissen, D., Shall, S. Regulation of DNA ligase activity by poly(ADP-ribose). Nature 296, 271–272 (1982). https://doi.org/10.1038/296271a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/296271a0
This article is cited by
-
Detection and quantification of poly-ADP-ribosylated cellular proteins of spleen and liver tissues of mice in vivo by slot and Western blot immunoprobing using polyclonal antibody against mouse ADP-ribose polymer
Molecular and Cellular Biochemistry (2005)
-
Recombination and its roles in DNA repair, cellular immortalization and cancer
AGE (1999)
-
Lesch‐Nyhan syndrome and its pathogenesis: Normal nicotinamide‐adenine dinucleotide but reduced ATP concentrations that correlate with reduced poly (ADP‐ribose) synthetase activity in HPRT‐deficient lymphoblasts
Journal of Inherited Metabolic Disease (1995)
-
Interaction of poly(ADP-ribose)polymerase with DNA polymerase ?
Molecular and Cellular Biochemistry (1994)
-
Growth-phase-dependent response to DNA damage in poly(ADP-ribose) polymerase deficient cell lines: basis for a new hypothesis describing the role of poly(ADP-ribose) polymerase in DNA replication and repair
Molecular and Cellular Biochemistry (1994)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.