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DNA Methyl Transferase Acting on O6-Methylguanine Residues in Adapted E. coli

  • Tomas Lindahl
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 40)

Abstract

Highly mutagenic alkylating agents such as N-methyl-N-nitrosourea (MNUA) or N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) produce three major puEine adducts in DNA: 7-methylguanine, 3-methyladenine, and O6-methylguanine (Lawley and Thatcher, 1970). These lesions are handled in different ways by living cells. The most abundant alkylation product, 7-methylguanine, is relatively harmless in that it does not cause an appreciable amount of miscoding, and in E. coli it does not seem to be actively removed by any repair pathway (Lawley and Orr, 1970). In contrast, 3-methyladenine is rapidly removed from DNA by an excision-repair process which is initiated by a speciqc DNA glycosylase that does not act on either 7-methylguanine or O6-methylguanine residues (giazuddin and Lindahl, 1978; Karran et al., 1980). The fate of O6-methyl-guanine in DNA has been less clear. While indications of active removal by a DNA repair process were obtained ten years ago by Lawley and Orr (1970), a DNA glycosylase catalyzing the release of such residues has not been found and may not exist. gurther, complete removal of the relatively large quantities of O6-methyl-guanine present in E. coli cells that have been treated with a high dose of MNNG is conspicuously less effective than the simultaneous liberation of 3-methyladenine from DNA.

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References

  1. Abbott, P.J., and Saffhill, R. (1979). Biochim. Biophys. Acta 562, 51–61.CrossRefGoogle Scholar
  2. Altamirano-Dimas, M., Sklar, R., and Strauss, B. (1979). Mut. Res. 60, 197–206.CrossRefGoogle Scholar
  3. Cairns, J. (1980). Nature 286, 176–178.CrossRefGoogle Scholar
  4. Goth, R., and Rajewsky, M.F. (1974). Proc. Natl. Acad. Sci. U.S. 71, 639–643.CrossRefGoogle Scholar
  5. Jeggo, P. (1979). J. Bact. 139, 783–791.Google Scholar
  6. Jeggo, P., Defais, M., Samson, L., and Schendel, P. (1977). Mol. Gen. Genetics 157, 1–9.CrossRefGoogle Scholar
  7. Jeggo, P., Defais, M., Samson, L., and Schendel, P. (1978). Mol. Gen. Genetics 162, 299–305.CrossRefGoogle Scholar
  8. Karran, P., Lindahl, T., and Griffin, B.E. (1979). Nature 280, 76–77.CrossRefGoogle Scholar
  9. Karran, P., Lindahl, T., Ofsteng, I., Evensen, G.B., and Seeberg, E. (1980). J. Mol. Biol. 140, 101–127.CrossRefGoogle Scholar
  10. Lawley, P.D., and Orr, D.J. (1970). Chem. Biol. Interact. 2, 154–157.CrossRefGoogle Scholar
  11. Lawley, P.D., and Thatcher, C.J. (1970). Biochem. J. 116, 693–707.CrossRefGoogle Scholar
  12. Mehta, J.R., and Ludlum, D.B. (1978). Biochim. Biophys. Acta 521, 770–778.CrossRefGoogle Scholar
  13. Montesano, R., Brésil, H., Planche-Martel, G., Margison, G.P., and Pegg, A.E. (1980). Cancer Res. 40, 452–458.PubMedGoogle Scholar
  14. Paik, W.K., and Kim, S. (1975). Adv. Enzymol. 42, 227–286PubMedGoogle Scholar
  15. Pegg, A.E. (1978). Biochem. Biophys. Res. Commun. 84, 166–173.CrossRefGoogle Scholar
  16. Radman, M. (1974). In “Molecular Mechanisms for Repair of DNA Part A”, ed. by P.C. Hanawalt and R.B. Setlow, pp. 355–367, Plenum Press, N.Y.Google Scholar
  17. Riazuddin, S., and Lindahl, T. (1978). Biochemistry 17, 2110–2118.CrossRefGoogle Scholar
  18. Robins, P., and Cairns, J. (1979). Nature 279, 74–76.CrossRefGoogle Scholar
  19. Samson, L., and Cairns, J. (1977). Nature 267, 281–283.CrossRefGoogle Scholar
  20. Schendel, P.F., Defais, M., Jeggo, P., Samson, L., and Cairns, J. (1978). J. Bact. 135, 466–475.PubMedPubMedCentralGoogle Scholar
  21. Schendel, P.F., and Robins, P.E. (1978). Proc. Natl. Acad. Sci. U.S. 75, 6017–6020.CrossRefGoogle Scholar
  22. Sedgwick, B., and Robins, P. (1981). This volume.Google Scholar
  23. Springer, M.S., Goy, M.F., and Adler, J. (1979). Nature 280, 279–284.CrossRefGoogle Scholar
  24. Warren, W., and Lawley, P.D. (1980). Carcinogenesis 1, 67–78.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Tomas Lindahl
    • 1
  1. 1.Department of Medical BiochemistryGothenburg UniversityGothenburgSweden

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