MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis (original) (raw)

Nature volume 355, pages 273–275 (1992)Cite this article

Abstract

ERRORS in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low1. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. This error-avoiding process is catalysed by a protein encoded by the_mutT_ gene of Escherichia coli, mutations of which increase the occurrence of A · T-→ C · G transversions 100 to 10,000 times the level of the wild type2. Spontaneous oxidation of dGTP forms 8-oxo-7,8-dihydro-2'-dGTP (8-oxodGTP), which is inserted opposite dA and dC residues of template DNA with almost equal efficiency, and the MutT protein specifically degrades 8-oxodGTP to the monophosphate. This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis.

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References

  1. Horiuchi, T., Maki, H. & Sekiguchi, M. Bull. Inst. Pasteur 87, 309–336 (1989).
    CAS Google Scholar
  2. Yanofsky, C., Cox, E. C. & Horn, V. Proc. natn. Acad. Sci. U.S.A. 55, 274–281 (1966).
    Article ADS CAS Google Scholar
  3. Akiyama, M., Maki, H., Sekiguchi, M. & Horiuchi, T. Proc. natn. Acad. Sci. U.S.A. 86, 3949–3952 (1989).
    Article ADS CAS Google Scholar
  4. Bhatnagar, S. K. & Bessman, M. J. biol. Chem. 263, 8953–8957 (1988).
    CAS PubMed Google Scholar
  5. Kasai, H. & Nishimura, S. Nucleic Acids Res. 12, 2137–2145 (1984).
    Article CAS Google Scholar
  6. Kasai, H. & Nishimura, S. in Oxidative Stress: Oxidants and Antioxidants (ed. Sies, H.), 99–116 (Academic, London, 1991).
    Google Scholar
  7. Shibutani, S., Takeshita, M. & Grollman, A. P. Nature 349, 431–434 (1991).
    Article ADS CAS Google Scholar
  8. Maki, H. & Kornberg, A. J. biol. Chem. 260, 12987–12992 (1985).
    CAS PubMed Google Scholar
  9. Sloane, D. L., Goodman, M. F. & Echols, H. Nucleic Acids Res. 16, 6465–6475 (1988).
    Article CAS Google Scholar
  10. Kasai, H., Tanooka, H. & Nishimura, S. Gann 75, 1037–1039 (1984).
    CAS PubMed Google Scholar
  11. Wood, M. L., Dizdaroglu, M., Gajewski, E. & Essigman, J. M. Biochemistry 29, 7024–7032 (1990).
    Article CAS Google Scholar
  12. Moriya, M. et al. Mutation Res. 254, 281–288 (1991).
    Article CAS Google Scholar
  13. Tchou, J. et al. Proc. natn. Acad. Sci. U.S.A. 88, 4690–4694 (1991).
    Article ADS CAS Google Scholar
  14. Cabrera, M., Nghiem, Y. & Miller, J. H. J. Bact. 170, 5405–5407 (1988).
    Article CAS Google Scholar
  15. Michaels, M. L., Pham, L., Cruz, C. & Miller, J. Nucleic Acids Res. 19, 3629–3632 (1988).
    Article Google Scholar
  16. Boosalis, M. S., Petruska, J. & Goodman, M. F. J. biol. Chem. 262, 14689–14696 (1987).
    CAS PubMed Google Scholar
  17. Fersht, A. in Enzyme Structure and Mechanism 91–92 (Freeman, San Francisco, 1977).
    Google Scholar
  18. Akiyama, M., Horiuchi, T. & Sekiguchi, M. Molec. gen. Genet. 206, 9–16 (1987).
    Article CAS Google Scholar
  19. Bradford, M. M. Analyt. Biochem. 72, 248–254 (1976).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Kyushu University, Fukuoka, 812, Japan
    Hisaji Maki & Mutsuo Sekiguchi

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  1. Hisaji Maki
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  2. Mutsuo Sekiguchi
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Maki, H., Sekiguchi, M. MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis.Nature 355, 273–275 (1992). https://doi.org/10.1038/355273a0

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