Nature 356, 356 - 358 (26 March 1992); doi:10.1038/356356a0

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

Masahiko S. Satoh & Tomas Lindahl

Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK

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)ation^6–8. 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 repair^10,11. 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.

References

1.	Chambon P., Weill, J. D., Doly, J., Strosser, M. T. & Mandel, P. Biochem. biophys. Res. Commun. 25, 638−643 (1966). | Article | ISI | ChemPort |
2.	Sugimura, T. Progr. Nucleic Acid Res. molec. Biol. 13, 127−151 (1973). | ChemPort |
3.	Ueda, K. & Hayaishi, O. A. Rev. Biochem. 54, 73−100 (1985). | Article | ChemPort |
4.	Althaus, F. R. & Richter, C. ADP-Ribosylation of Proteins, Enzymology and Biological Significance 1−125 (Springer, Berlin, 1987). | ChemPort |
5.	Cleaver, J. E. & Morgan, W. F. Mut. Res. 257, 1−18 (1991). | ChemPort |
6.	Kameshita, I., Matsuda, Z., Taniguchi, T. & Shizuta, Y. J. biol. Chem. 259, 4770−4776 (1984). | PubMed | ChemPort |
7.	Gradwohl, G. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2990−2994 (1990). | ChemPort |
8.	Desmarais, Y., Menard, L., Lagueux, J. & Poirier, G. G. Biochim. biophys. Acta 1078, 179−186 (1991). | PubMed | ChemPort |
9.	Miwa, M. & Sigimura, T. Meth. Enzym. 106, 441−450 (1984). | PubMed | ChemPort |
10.	Durkacz, B. W., Omidji, O., Gray, D. A. & Shall, S. Nature 283, 593−596 (1980). | Article | PubMed | ISI | ChemPort |
11.	Shall, S. Adv. Radiat. Biol. 11, 1−69 (1984). | ChemPort |
12.	Wood, R. D., Robins, P. & Lindahl, T. Cell 53, 97−106 (1988). | Article | PubMed | ISI | ChemPort |
13.	Manley, J. L., Fire, A., Samuels, M. & Sharp, P. A. Meth. Enzym. 101, 568−582 (1983). | Article | PubMed | ISI | ChemPort |
14.	Nduka, N., Skidmore, C. J. & Shall, S. Eur. J. Biochem. 105, 525−530 (1980). | Article | PubMed | ISI | ChemPort |
15.	Ben-Hur, E., Utsumi, H. & Elkind, M. M. Radiat Res. 97, 546−555 (1984). | PubMed | ChemPort |
16.	Smith, S. & Stillman, B. EMBO J. 10, 971−980 (1991). | PubMed | ISI | ChemPort |
17.	Yoshihara, K. et al. J. biol. Chem. 256, 3471−3478 (1981). | PubMed | ChemPort |
18.	Ferro, A. M. & Olivera, B. M. J. biol. Chem. 257, 7808−7813 (1982). | PubMed | ChemPort |
19.	Zahradka, P. & Ebisuzaki, K. Eur. J. Biochem. 127, 579−585 (1982). | PubMed | ISI | ChemPort |
20.	Zahradka, P. & Ebisuzaki, K. Eur. J. Biochem. 142, 503−509 (1984). | Article | PubMed | ChemPort |
21.	Eki, T. & Hurwitz, J. J. biol. Chem. 266, 3087−3100 (1991). | PubMed | ChemPort |
22.	Yoshihara, K. et al. Biochem. biophys. Res. Commun. 128, 61−67 (1985). | Article | PubMed | ChemPort |
23.	Werner, E. et al. Eur. J. Biochem. 139, 81−86 (1984). | Article | PubMed | ChemPort |
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). | ChemPort |
25.	Slattery, E., Dignam, J. D., Matsui, T. & Roeder, R. G. J. biol. Chem. 258, 5955−5959 (1983). | PubMed | ISI | ChemPort |