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Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG


OXIDATIVE damage to DNA, reflected in the formation of 8-oxo- 7-hydrodeoxyguanosine (8-oxodG)1,2, may be important in mutagenesis, carcinogenesis and the ageing process3,4. Kuchino et al. studied DNA synthesis on oligodeoxynucleotide templates containing 8-oxodG, concluding that the modified base lacked base pairing specificity and directed misreading of pyrimidine residues neighbouring the lesion5. Here we report different results, using an approach in which the several products of a DNA polymerase reaction can be measured. In contrast to the earlier report5, we find that dCMP and dAMP are incorporated selectively opposite 8-oxodG with transient inhibition of chain extension occurring 3' to the modified base. The potentially mutagenic insertion of dAMP is targeted exclusively to the site of the lesion. The ratio of dCMP to dAMP incorporated varies, depending on the DNA polymerase involved. Chain extension from the dA · 8-oxodG pair was efficiently catalysed by all polymerases tested.

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  1. Kasai, H. & Nishimura, S. Nucleic Acid Res. 12, 2137–2145 (1984).

    Article  CAS  Google Scholar 

  2. Shigenaga, M. K., Gimeno, C. J. & Ames, B. N. Proc. natn. Acad. Sci. U.S.A. 86, 9697–9701 (1989).

    Article  ADS  CAS  Google Scholar 

  3. Harman, D. Proc. natn. Acad. Sci. U.S.A. 78, 7124–7128 (1981).

    Article  ADS  CAS  Google Scholar 

  4. Ames, B. N. Science 221, 1256–1264 (1983).

    Article  ADS  CAS  Google Scholar 

  5. Kuchino, Y. et al. Nature 327, 77–79 (1987).

    Article  ADS  CAS  Google Scholar 

  6. Maxam, A. M. & Gilbert, W. Meth. Enzymol. 65, 499–560 (1980).

    Article  CAS  Google Scholar 

  7. Mendelman, L. V., Petruska, J. & Goodman, M. F. J. biol. chem. 264, 14415–14423 (1989).

    CAS  PubMed  Google Scholar 

  8. Mendelman, L. V., Petruska, J. & Goodman, M. F. J. biol. Chem. 265, 2338–2346 (1990).

    CAS  PubMed  Google Scholar 

  9. Loeb, L. A. & Kunkel, T. A. A. Rev. Biochem. 52, 429–457 (1982).

    Article  Google Scholar 

  10. Kunkel, T. A. Cell 53, 837–840 (1988).

    Article  CAS  Google Scholar 

  11. Kasai, H., Nishimura, S., Toriumi, Y., Itai, A. & Iitaka, Y. Bull. Chem. Soc. Jpn 60, 3799–3800 (1987).

    Article  CAS  Google Scholar 

  12. Aida, M. & Nishimura, S. Mut. Res. 192, 83–89 (1987).

    Article  CAS  Google Scholar 

  13. Culp, S. J., Cho, B. P., Kadlubar, F. F. & Evans, F. E. Chem. Res. Toxicol. 2, 416–422 (1989).

    Article  CAS  Google Scholar 

  14. Uesugi, J. & Ikehama, M. J. Am. Chem. Soc. 99, 3250–3253 (1977).

    Article  CAS  Google Scholar 

  15. Kouchakdjian, M. et al. J. Biochemistry (in the press).

  16. Wood, M. L., Dizdaroglu, M., Gajewski, E. & Essigmann, J. M. Biochemistry 29, 7024–7032 (1990).

    Article  CAS  Google Scholar 

  17. Bodepudi, V., Iden, C. R. & Johnson, F. Nucleosides and Nucleotides (in the press).

  18. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning 13.73–13.77 (Cold Spring Harbor Press, New York, 1989).

    Google Scholar 

  19. Abbots, J. et al. Biochemistry 27, 901–909 (1988).

    Article  Google Scholar 

  20. Karawya, E. M. & Wilson, S. H. J. biol. Chem. 257, 13129–13134 (1982).

    CAS  PubMed  Google Scholar 

  21. Lee, M. Y. W. T., Tan, C.-K., Downey, K. M. & So, A. G. Biochemistry 23, 1906–1913 (1984).

    Article  CAS  Google Scholar 

  22. Tan, C.-K., Castillo, C., So, A. G. & Downey, K. M. J. biol. Chem. 261, 12310–12316 (1986).

    CAS  PubMed  Google Scholar 

  23. Moriya, M. et al. Mut. Res. (in the press).

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Shibutani, S., Takeshita, M. & Grollman, A. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature 349, 431–434 (1991).

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