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Mammalian Enzymes for Preventing Mutations Caused by Oxidation of Guanine Nucleotides

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DNA Damage and Repair

Part of the book series: Contemporary Cancer Research ((CCR))

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Abstract

Oxygen radicals are produced through normal cellular metabolism, and formation of such radicals is further enhanced by ionizing radiation and by various chemicals (3). The oxygen radicals attack nucleic acids and generate various modified bases in DNA (9, 16). Among them, 8-oxo-7,8-dihydroguanine (8-oxoG) is the most abundant, and appears to play critical roles in carcinogenesis and in aging (6, 22). 8-OxoG can pair with both cytosine and adenine during DNA synthesis, and as a result, G-C to T-A transversions are induced (28, 31). Oxidation of guanine also occurs in the cellular nucleotide pool. 8-Oxo-dGTP thus formed is a potent mutagenic substrate for DNA synthesis, since it can be incorporated opposite adenine as well as cytosine in DNA, at almost equal efficiencies (24). In this case, both types of transversions, A-T to C-G and G-C to T-A, would be induced (13).

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References

  1. Akiyama, M., T. Horiuchi, and M. Sekiguchi. 1987. Molecular cloning and nucleotide sequence of the mutT mutator of Escherichia coli that causes A:T to C:G transversion. Mol. Gen. Genet. 206: 9–16.

    Article  PubMed  CAS  Google Scholar 

  2. Akiyama, M., H. Maki, M. Sekiguchi, and T. Horiuchi. 1989. A specific role of MutT protein: To prevent dG•dA mispairing in DNA replication. Proc. Natl. Acad. Sci. USA 86: 3949–3952.

    Article  PubMed  CAS  Google Scholar 

  3. Ames, B. N. and L. S. Gold. 1991. Endogenous mutagens and the causes of aging and cancer. Mutat. Res. 250: 3–16.

    Article  PubMed  CAS  Google Scholar 

  4. Au, K. G., M. Cabrera, J. H. Miller, and P. Modrich. 1988. Escherichia coli mutY gene product is required for specific A•G C•G mismatch correction. Proc. Natl. Acad. Sci. USA 85: 9163–9166.

    Article  CAS  Google Scholar 

  5. Au, K. G., S. Clark, J. H. Miller, and P. Modrich. 1989. Escherichia coli mutY gene encodes an adenine glycosylase active on G-A mispairs. Proc. Natl. Acad. Sci. USA 86: 8877–8881.

    Article  CAS  Google Scholar 

  6. Bessho, T., K. Tano, H. Kasai, and S. Nishimura. 1992. Deficiency of 8-hydroxyguanine DNA endonuclease activity and accumulation of the 8-hydroxyguanine in mutator mutant (mutM) of Escherichia coli. Biochem. Biophys. Res. Commun. 188: 372–378.

    Article  CAS  Google Scholar 

  7. Bessho, T., K. Tano, H. Kasai, E. Ohtsuka, and S. Nishimura. 1993. Evidence for two DNA repair enzymes for 8-hydroxyguanine(7,8-dihydro-8-oxoguanine) in human cells. J. Biol. Chem. 268: 19,416–19, 421.

    Google Scholar 

  8. Bessho, T., R. Roy, K. Yamamoto, H. Kasai, S. Nishimura, K. Tano, and S. Mitra. 1993. Repair of 8-hydroxyguanine in DNA by mammalian N-methylpurine-DNA glycosylase. Proc. Natl. Acad. Sci. USA 90: 8901–8904.

    Article  PubMed  CAS  Google Scholar 

  9. Boiteux, S., E. Gajewski, J. Laval, and M. Dizdaroglu. 1992. Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry 31: 106–110.

    Article  PubMed  CAS  Google Scholar 

  10. Bullions, L. C., V. Méjean, J.-P. Claverys, and M. J. Bessman. 1994. Purification of the MutX protein of Streptococcus pneumoniae, a homologue of Escherichia coli MutT. J. Biol. Chem. 269: 12,339–12, 344.

    Google Scholar 

  11. Cabrera, M., Y. Nghiem, and J. H. Miller. 1988. mutM, a second mutator locus in Escherichia coli that generates GC transversions. J. Bacteriol. 170: 5405–5407.

    Google Scholar 

  12. Cai, J.-P., T. Kakuma, T. Tsuzuki, and M. Sekiguchi. 1995. cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides. Carcinogenesis 16: 2343–2350.

    Google Scholar 

  13. Cheng, K. C., D. S. Cahill, H. Kasai, S. Nishimura, and L. A. Loeb. 1992. 8Hydroxyguanine, an abundant form of oxidative DNA damage, causes G–T and A–C substitutions. J. Biol. Chem. 267: 166–172.

    Google Scholar 

  14. Chung, M. H., H. Kasai, D. S. Jones, H. Inoue, H. Ishikawa, E. Ohtsuka, and S. Nishimura. 1991. An endonuclease activity of Escherichia coli that specifically removes 8hydroxyguanine residues from DNA. Mutat. Res. 254: 1–12.

    Article  PubMed  CAS  Google Scholar 

  15. Furuichi, M., M. C. Yoshida, H. Oda, T. Tajiri, Y. Nakabeppu, T. Tsuzuki, and M. Sekiguchi. 1994. Genomic structure and chromosome location of the human mutT homologue gene MTHI encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion. Genomics 24: 485–490.

    Article  PubMed  CAS  Google Scholar 

  16. Gajewski, E., G. Rao, Z. Nackerdien, and M. Dizdaroglu. 1990. Modification of DNA bases in mammalian chromatin by radiation-generated free radicals. Biochemistry 29: 7876–7882.

    Article  PubMed  CAS  Google Scholar 

  17. Hayakawa, H., A. Taketomi, K. Sakumi, M. Kuwano, and M. Sekiguchi. 1995. Generation and elimination of 8-oxo-7,8-dihydro-2’-deoxyguanosine 5’-triphosphate, a mutagenic substrate for DNA synthesis, in human cells. Biochemistry 34: 89–95.

    Article  PubMed  CAS  Google Scholar 

  18. Ionov, Y., M. A. Peinado, S. Malkhosyan, D. Shibata, and M. Perucho. 1993. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363: 558–561.

    Article  PubMed  CAS  Google Scholar 

  19. Kakuma, T., J. Nishida, T. Tsuzuki, and M. Sekiguchi. 1995. Mouse MTH 1 protein with 8-oxo-7,8-dihydro-2’-deoxyguanosine 5’-triphosphatase activity that prevents transversion mutation. J. Biol. Chem. 270: 25,942–25, 948.

    Google Scholar 

  20. Kamath, A. V. and C. Yanofsky. 1993. Sequence and characterization of mutT from Proteus vulgaris. Gene 134: 99–102.

    Article  CAS  Google Scholar 

  21. Kang, D., J. Nishida, A. Iyama, Y. Nakabeppu, M. Furuichi, T. Fujiwara, M. Sekiguchi, and K. Takeshige. 1995. Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria. J. Biol. Chem. 270: 14,659–14, 665.

    Google Scholar 

  22. Kasai, H., P. F. Crain, Y. Kuchino, S. Nishimura, A. Ootsuyama, and H. Tanooka. 1986. Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair. Carcinogenesis 7: 1849–1851.

    Article  PubMed  CAS  Google Scholar 

  23. Loeb, L. A. 1994. Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res. 54: 5059–5063.

    PubMed  CAS  Google Scholar 

  24. Maki, H. and M. Sekiguchi. 1992. MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature 355: 273–275.

    Article  PubMed  CAS  Google Scholar 

  25. Michaels, M. L., L. Pham, C. Cruz, and J. H. Miller. 1991. MutM, a protein that prevents G•C T A transversions, is formamidopyrimidine-DNA glycosylase. Nucleic Acids Res. 19: 3629–3632.

    Article  PubMed  CAS  Google Scholar 

  26. Michaels, M. L., C. Cruz, A. P. Grollman, and J. H. Miller. 1992. Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. Proc. Natl. Acad. Sci. USA 89: 7022–7025.

    Article  PubMed  CAS  Google Scholar 

  27. Mo, J.-Y., H. Maki, and M. Sekiguchi. 1992. Hydrolytic elimination of a mutagenic nucleotide, 8-oxodGTP, by human 18-kilodalton protein: sanitization of nucleotide pool. Proc. Natl. Acad. Sci. USA 89: 11,021–11, 025.

    Google Scholar 

  28. Moriya, M. 1993. Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-Oxoguanine in DNA induces targeted G•C — T A transversions in simian kidney cells. Proc. Natl. Acad. Sci. USA 90: 1122–1126.

    Article  PubMed  CAS  Google Scholar 

  29. Nghiem, Y., M. Cabrera, C. G. Cupples, and J. H. Miller. 1988. The mutY gene: A mutator locus in Escherichia coli that generates G•C -* T A transversions. Proc. Natl. Acad. Sci. USA 85: 2709–2713.

    Article  PubMed  CAS  Google Scholar 

  30. Sakumi, K., M. Furuichi, T. Tsuzuki, T. Kakuma, S. Kawabata, H. Maki, and M. Sekiguchi. 1993. Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substate for DNA synthesis. J. Biol. Chem. 268: 23,524–23, 530.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Tajiri, T., H. Maki, and M. Sekiguchi. 1995. Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli. Mutat. Res. 336: 257–267.

    Article  CAS  Google Scholar 

  33. Tchou, J. and A. P. Grollman. 1993. Repair of DNA containing the oxidatively-damaged base, 8-oxoguanine. Mutat. Res. 299: 277–287.

    Article  PubMed  CAS  Google Scholar 

  34. Weber, D. J., C. Abeygunawardana, M. J. Bessman, and A. S. Mildvan. 1993. Secondary structure of the MutT enzyme as determined by NMR. Biochemistry 32: 13, 081–13, 088.

    Google Scholar 

  35. Yanofsky, C., E. C. Cox, and V. Horn. 1966. The unusual mutagenic specificity of an E. coli mutator gene. Proc. Natl. Acad. Sci. USA 55: 274–281.

    Article  PubMed  CAS  Google Scholar 

  36. Yeh, Y.-C., D.-Y. Chang, J. Masin, and A.-L. Lu. 1991. Two nicking enzyme systems specific for mismatch-containing DNA in nuclear extracts from human cells. J. Biol. Chem. 266: 6480–6484.

    PubMed  CAS  Google Scholar 

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Authors
  1. Mutsuo Sekiguchi
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  2. Hiroshi Hayakawa
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Editor information

Editors and Affiliations

  1. University of New Mexico, Albuquerque, NM, USA

    Jac A. Nickoloff

  2. Signal Pharmaceuticals, San Diego, CA, USA

    Merl F. Hoekstra

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Sekiguchi, M., Hayakawa, H. (1998). Mammalian Enzymes for Preventing Mutations Caused by Oxidation of Guanine Nucleotides. In: Nickoloff, J.A., Hoekstra, M.F. (eds) DNA Damage and Repair. Contemporary Cancer Research. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-455-9_6

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  • DOI: https://doi.org/10.1007/978-1-59259-455-9_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5015-7

  • Online ISBN: 978-1-59259-455-9

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