Abstract
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.
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
Kasai, H. & Nishimura, S. Nucleic Acid Res. 12, 2137–2145 (1984).
Shigenaga, M. K., Gimeno, C. J. & Ames, B. N. Proc. natn. Acad. Sci. U.S.A. 86, 9697–9701 (1989).
Harman, D. Proc. natn. Acad. Sci. U.S.A. 78, 7124–7128 (1981).
Ames, B. N. Science 221, 1256–1264 (1983).
Kuchino, Y. et al. Nature 327, 77–79 (1987).
Maxam, A. M. & Gilbert, W. Meth. Enzymol. 65, 499–560 (1980).
Mendelman, L. V., Petruska, J. & Goodman, M. F. J. biol. chem. 264, 14415–14423 (1989).
Mendelman, L. V., Petruska, J. & Goodman, M. F. J. biol. Chem. 265, 2338–2346 (1990).
Loeb, L. A. & Kunkel, T. A. A. Rev. Biochem. 52, 429–457 (1982).
Kunkel, T. A. Cell 53, 837–840 (1988).
Kasai, H., Nishimura, S., Toriumi, Y., Itai, A. & Iitaka, Y. Bull. Chem. Soc. Jpn 60, 3799–3800 (1987).
Aida, M. & Nishimura, S. Mut. Res. 192, 83–89 (1987).
Culp, S. J., Cho, B. P., Kadlubar, F. F. & Evans, F. E. Chem. Res. Toxicol. 2, 416–422 (1989).
Uesugi, J. & Ikehama, M. J. Am. Chem. Soc. 99, 3250–3253 (1977).
Kouchakdjian, M. et al. J. Biochemistry (in the press).
Wood, M. L., Dizdaroglu, M., Gajewski, E. & Essigmann, J. M. Biochemistry 29, 7024–7032 (1990).
Bodepudi, V., Iden, C. R. & Johnson, F. Nucleosides and Nucleotides (in the press).
Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning 13.73–13.77 (Cold Spring Harbor Press, New York, 1989).
Abbots, J. et al. Biochemistry 27, 901–909 (1988).
Karawya, E. M. & Wilson, S. H. J. biol. Chem. 257, 13129–13134 (1982).
Lee, M. Y. W. T., Tan, C.-K., Downey, K. M. & So, A. G. Biochemistry 23, 1906–1913 (1984).
Tan, C.-K., Castillo, C., So, A. G. & Downey, K. M. J. biol. Chem. 261, 12310–12316 (1986).
Moriya, M. et al. Mut. Res. (in the press).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1038/349431a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/349431a0
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.
