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Role of poly(ADP-ribose) formation in DNA repair

Abstract

THE abundant nuclear enzyme poly(ADP-ribose) polymerase catalyses the synthesis of poly(ADP-ribose) from nicotinamide adenine dinucleotide (NAD+)1–5. This protein has an N-terminal DNA-binding domain containing two zinc-fingers, which is linked to the C-terminal NAD+-binding domain by a short region containing several glutamic acid residues that are sites of auto-poly(ADP-ribosyl)ation6–8. The intracellular production of poly(ADP-ribose) is induced by agents that generate strand interruptions in DNA7. The branched homopolymer chains may attain a size of 200–300 residues9 but are rapidly degraded after synthesis. The function of poly(ADP-ribose) synthesis is not clear, although it seems to be required for DNA repair10,11. Here we describe a human cell-free system that enables the role of poly(ADP-ribose) synthesis in DNA repair to be characterized. The results indicate that unmodified polymerase molecules bind tightly to DNA strand breaks; auto-poly(ADP-ribosyl)ation of the protein then effects its release and allows access to lesions for DNA repair enzymes.

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References

  1. Chambon P., Weill, J. D., Doly, J., Strosser, M. T. & Mandel, P. Biochem. biophys. Res. Commun. 25, 638–643 (1966).

    Article  CAS  Google Scholar 

  2. Sugimura, T. Progr. Nucleic Acid Res. molec. Biol. 13, 127–151 (1973).

    Article  CAS  Google Scholar 

  3. Ueda, K. & Hayaishi, O. A. Rev. Biochem. 54, 73–100 (1985).

    Article  CAS  Google Scholar 

  4. Althaus, F. R. & Richter, C. ADP-Ribosylation of Proteins, Enzymology and Biological Significance 1–125 (Springer, Berlin, 1987).

    Book  Google Scholar 

  5. Cleaver, J. E. & Morgan, W. F. Mut. Res. 257, 1–18 (1991).

    Article  CAS  Google Scholar 

  6. Kameshita, I., Matsuda, Z., Taniguchi, T. & Shizuta, Y. J. biol. Chem. 259, 4770–4776 (1984).

    CAS  PubMed  Google Scholar 

  7. Gradwohl, G. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2990–2994 (1990).

    Article  ADS  CAS  Google Scholar 

  8. Desmarais, Y., Menard, L., Lagueux, J. & Poirier, G. G. Biochim. biophys. Acta 1078, 179–186 (1991).

    Article  CAS  Google Scholar 

  9. Miwa, M. & Sigimura, T. Meth. Enzym. 106, 441–450 (1984).

    Article  CAS  Google Scholar 

  10. Durkacz, B. W., Omidji, O., Gray, D. A. & Shall, S. Nature 283, 593–596 (1980).

    Article  ADS  CAS  Google Scholar 

  11. Shall, S. Adv. Radiat. Biol. 11, 1–69 (1984).

    Article  CAS  Google Scholar 

  12. Wood, R. D., Robins, P. & Lindahl, T. Cell 53, 97–106 (1988).

    Article  CAS  Google Scholar 

  13. Manley, J. L., Fire, A., Samuels, M. & Sharp, P. A. Meth. Enzym. 101, 568–582 (1983).

    Article  CAS  Google Scholar 

  14. Nduka, N., Skidmore, C. J. & Shall, S. Eur. J. Biochem. 105, 525–530 (1980).

    Article  CAS  Google Scholar 

  15. Ben-Hur, E., Utsumi, H. & Elkind, M. M. Radiat Res. 97, 546–555 (1984).

    Article  ADS  CAS  Google Scholar 

  16. Smith, S. & Stillman, B. EMBO J. 10, 971–980 (1991).

    Article  CAS  Google Scholar 

  17. Yoshihara, K. et al. J. biol. Chem. 256, 3471–3478 (1981).

    CAS  PubMed  Google Scholar 

  18. Ferro, A. M. & Olivera, B. M. J. biol. Chem. 257, 7808–7813 (1982).

    CAS  PubMed  Google Scholar 

  19. Zahradka, P. & Ebisuzaki, K. Eur. J. Biochem. 127, 579–585 (1982).

    Article  CAS  Google Scholar 

  20. Zahradka, P. & Ebisuzaki, K. Eur. J. Biochem. 142, 503–509 (1984).

    Article  CAS  Google Scholar 

  21. Eki, T. & Hurwitz, J. J. biol. Chem. 266, 3087–3100 (1991).

    CAS  PubMed  Google Scholar 

  22. Yoshihara, K. et al. Biochem. biophys. Res. Commun. 128, 61–67 (1985).

    Article  CAS  Google Scholar 

  23. Werner, E. et al. Eur. J. Biochem. 139, 81–86 (1984).

    Article  CAS  Google Scholar 

  24. Poirier, G. G., de Murcia, G., Jongstra-Bilen, J., Niedergang, C. & Mandel, P. Proc. natn. Acad. Sci. U.S.A. 79, 3423–3427 (1982).

    Article  ADS  CAS  Google Scholar 

  25. Slattery, E., Dignam, J. D., Matsui, T. & Roeder, R. G. J. biol. Chem. 258, 5955–5959 (1983).

    CAS  PubMed  Google Scholar 

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Satoh, M., Lindahl, T. Role of poly(ADP-ribose) formation in DNA repair. Nature 356, 356–358 (1992). https://doi.org/10.1038/356356a0

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