Abstract
Chromatin proteins are covalently modified by at least five different processes; in no case has the precise physiological function been established. One of these post-synthetic, covalent modifications is effected by the enzyme poly(ADP–ribose) polymerase, which uses the coenzyme NAD+ to ADP–ribosylate chromatin proteins1–3. The modification consists largely of mono(ADP–ribose), but long, homopolymer chains of (ADP–ribose) are also present. Various physiological functions have been suggested for (ADP–ribose)n. Here we demonstrate that one function of (ADP–ribose)n is to participate in the cellular recovery from DNA damage. Specific inhibitors of poly(ADP–ribose) polymerase prevent rejoining of DNA strand breaks caused by dimethyl sulphate and cytotoxicity is enhanced thereby. The rejoining of strand breaks is prevented also by nutritionally depleting the cells of NAD.
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Hilz, H. & Stone, P. Rev. Physiol. Biochem. Pharmac. 76, 1–58 (1976).
Hayaishi, O. & Ueda, K. A. Rev. Biochem. 46, 95–116 (1977).
Tsopanakis, C., Leeson, E., Tsopanakis, A. & Shall, S. Eur. J. Biochem. 90, 337–345 (1978).
Campagnari, F., Whitfield, J. F. & Bertazzoni, U. Expl Cell. Res. 42, 646–656 (1966).
Scaife, J. F. Can. J. Biochem. Physiol. 41, 1469–1481 (1963).
Hilz, H., Hlavica, P. & Bertram, B. Biochem. Z. 338, 283–299 (1963).
Roitt, I. M. Biochem. J. 63, 300–307 (1956).
Schein, P. S., Cooney, D. A. & Vernon, M. L. Cancer Res. 27, 2323–2332 (1967).
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).
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).
Berger, N. A., Sikorski, G. W., Petzold, S. J. & Kurohara, K. K. (in preparation).
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. 88, 144–146 (1978).
Khan, M. G. thesis, Univ. Sussex (1977).
Shall, S. J. Biochem., Tokyo 77, 2p (1975).
Jacobson, E. L., Lange, R. A. & Jacobson, M. K. J. cell. Physiol. 99, 417–426 (1979).
Berger, N. A., Weber, G. & Kaichi, A. S. Biochim. biophys. Acta 519, 87–104 (1978).
Yoshihara, K., Tanigawa, Y., Burzio, L. & Koide, S. S. Proc. natn. Acad. Sci. U.S.A. 72, 289–293 (1975).
Stone, P. R., Lorimer, W. S. & Kidwell, W. R. Eur. J. Biochem. 81, 9–18 (1977).
Lorimer, W. S., Stone, P. R. & Kidwell, W. R. Expl Cell Res. 106, 261–266 (1977).
Byrne, R. H., Stone, P. R. & Kidwell, W. R. Expl Cell Res. 115, 277–283 (1978).
Perella, F. W. & Lea, M. A. Biochem. biophys. Res. Commun. 82, 575–581 (1978).
Perella, F. W. & Lea, M. A. Cancer Res. 39, 1382–1389 (1979).
Mortelmans, K., Friedberg, E. C., Slor, H., Thomas, G. & Cleaver, J. E. Proc. natn. Acad. Sci. U.S.A. 73, 2757–2761 (1976).
Jacobson, E. L. & Narasimhan, G. Fedn Proc. 38, 619 (abstr. 2065) (1979).
Juarez-Salinas, H., Sims, J. L. & Jacobson, M. K. Nature 282, 740–741 (1979).
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Durkacz, B., Omidiji, O., Gray, D. et al. (ADP-ribose)n participates in DNA excision repair. Nature 283, 593–596 (1980). https://doi.org/10.1038/283593a0
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DOI: https://doi.org/10.1038/283593a0
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