Molecular and General Genetics MGG

, Volume 179, Issue 1, pp 191–199 | Cite as

Defective excision repair in a mutant of Micrococcus radiodurans hypermutable by some monofunctional alkylating agents

  • Philip R. Tempest
  • Bevan E. B. Moseley
Article
Received:

Summary

The lethal and mutagenic effects of methyl methanesulphonate (MMS), ethyl methanesulphonate (EMS), and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) can be dissociated in a mitomycin C (MTC)-sensitive mutant, strain 302, of Micrococcus radiodurans.

As regards lethality 302 is extremely sensitive, compared with the wild type, to MTC and decarbamoyl MTC (DCMTC), slightly sensitive to EMS, MNNG, nitrous acid, 7-bromomethylbenz {α} anthracene (BrMBA), and N-acetoxy-N-2-acetylaminofluorene (AAAF), and resistant to MMS, hydroxylamine, and ICR 191G. As regards mutability it is, compared to the wild type, very sensitive to MMS, EMS, and MNNG, and slightly sensitive to hydroxylamine and nitrous acid but not to any other agent examined.

Alkaline sucrose gradient studies indicate that 302 does not incise DNA containing BrMBA adducts, although it does incise DNA damaged by AAAF but probably not to the same extent as wild type.

We put forward the hypothesis that the hypermutability of 302 is due to the non-removal of bases or nucleotides, modified in exocyclic positions, which have altered base-pairing capabilities, while lethality results from the non-removal of bases or nucleotides, also modified in exocyclic positions, which no longer form hydrogen-bonded base pairs.

Keywords

Nitrous Acid Anthracene Mitomycin Hydroxylamine Excision Repair 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson, A.W., Nordan, H.C., Cain, R.F., Parrish, G., Duggan, D.: Studies on a radio-resistant micrococcus. I. Isolation morphology, cultural characteristics, and resistance to gamma radiation. Food Technol. 10, 575–578 (1956)Google Scholar
  2. Beland, F.A.: Computer-generated graphic models of the N 2-substituted deoxyguanosine adducts of 2-acetalyaminofluorene and benzo(α)pyrene and the O 6-subtituted deoxyguanosine adduct of 1-naphthylamine in the DNA double helix. Chem.-biol. Interact. 22, 329–339 (1978)Google Scholar
  3. Bridges, B.A., Mottershead, R.P., Green, M.H.L., Gray, W.J.H.: Mutagenicity of dichlorvos and methyl methanesulphonate for Escherichia coli WP2 and some derivatives deficient in DNA repair. Mutation Res. 19, 295–303 (1973)Google Scholar
  4. Budowsky, E.I.: The mechanism of the mutagenic action of hydroxylamines. Prog. Nucleic Acid Res. Mol. Biol. 16, 125–188 (1976)Google Scholar
  5. Cerutti, P.A.: Repairable damage in DNA: Overview. In: Molecular mechanisms for repair of DNA (P.C. Hanawalt and R.B. Setlow, eds.), pp. 3–12. New York: Plenum Press 1975Google Scholar
  6. Dipple, A., Brookes, P., Mackintosh, D.S., Rayman, M.P.: Reaction of 7-bromomethylbenz(α)anthracene with nucleic acids, polynucleotides and nucleosides. Biochemistry 10, 4323–4330 (1971)Google Scholar
  7. Drake, J.W., Baltz, R.H.: The biochemistry of mutagenesis. Ann. Rev. Biochem. 45, 11–37 (1976)Google Scholar
  8. Duggan, D.E., Anderson, A.W., Elliker, P.R., Cain, R.F.: Ultraviolet exposure studies on a gamma radiation resistant micrococcus isolated from food. Food Res. 24, 376–382 (1959)Google Scholar
  9. Freese, E.: Molecular mechanisms of mutations. In: Chemical mutagens. Principles and methods for their detection (A. Hollaender, ed.), Vol. 1, pp. 1–56. New York and London: Plenum Press 1971Google Scholar
  10. Gerchman, L.L., Ludlum, D.B.: The properties of O 6-methylguanine in templates for RNA polymerase. Biochim. Biophys. Acta 308, 310–316 (1973)Google Scholar
  11. Glickman, B., Elsen, P. van den, Radman, M.: Induced mutagenesis in dam − mutants of Escherichia coli: a role for 6-methyladenine residues in mutation avoidance. Mol. Gen. Genet. 163, 307–312 (1978)Google Scholar
  12. Green, M.H.L., Muriel, W.J., Bridges, B.A.: Use of a simplified fluctuation test to detect low levels of mutagens. Mutat. Res. 38, 33–42 (1976)Google Scholar
  13. Grunberger, D., Blobstein, S.H., Weinstein, I.B.: Modification of ribonucleic acid by chemical carcinogens. VI. Effect of N-2-acetylaminofluorene modification of guanosine on the codon function of adjacent nucleosides in oligonucleotides. J. Mol. Biol. 82, 459–468 (1974)Google Scholar
  14. Hecht, R., Thielmann, H.W.: Purification and characterization of an endonuclease from Micrococcus luteus that acts on depurinated and carcinogen-modified DNA. Eur. J. Biochem. 89, 607–618 (1978)Google Scholar
  15. Ishii, Y., Kondo, S.: Comparative analysis of deletion and basechange mutabilities of Escherichia coli B strains differing in DNA repair capacity (wild-type, uvrA −, polA −, recA −) by various mutagens. Mutat. Res. 27, 27–44 (1975)Google Scholar
  16. Kerszman, G.: Induction of mutation to streptomycin resistance in Micrococcus radiodurans. Mutat. Res. 28, 9–14 (1975)Google Scholar
  17. Kondo, S., Ichikawa, H., Iwo, K., Kato, T.: Base-change mutagenesis and prophage induction in strains of Escherichia coli with different DNA repair capacities. Genetics 66, 187–217 (1970)Google Scholar
  18. Mehta, J.R., Ludlum, D.B.: Synthesis and properties of O 6-methylguanylic acid and its copolymers with deoxycytidylic acid. Biochim. Biophys. Acta 521, 770–778 (1978)Google Scholar
  19. Michelson, A.M., Monny, C.: Polynucleotide analogues. IX. Polyxanthylic acid. Biochim. Biophys. Acta 129, 460–474 (1966)Google Scholar
  20. Moseley, B.E.B., Copland, H.J.R.: Four mutants of Micrococcus radiodurans defective in the ability to repair DNA damaged by mitomycin C, two of which have wild-type resistance to ultraviolet radiation. Mol. Gen. Genet. 160, 331–337 (1978)Google Scholar
  21. Murayama, I., Otsuji, N.: Mutation by mitomycins in the ultraviolet light-sensitive mutant of Escherichia coli. Mutat. Res. 18, 117–119 (1973)Google Scholar
  22. Newton, A., Masys, D., Leonardi, E., Wygal, D.: Association of induced frameshift mutagenesis and DNA replication in Escherichia coli. Nature (London) New Biol. 236, 19–22 (1972)Google Scholar
  23. Sweet, D.M., Moseley, B.E.B.: Accurate repair of ultraviolet-induced damage in Micrococcus radiodurans. Mutat. Res. 23, 311–318 (1974)Google Scholar
  24. Sweet, D.M., Moseley, B.E.B.: The resistance of Micrococcus radiodurans to killing and mutation by agents which damage DNA. Mutat. Res. 34, 175–186 (1976)Google Scholar
  25. Szybalski, W., Iyer, V.N.: Crosslinking of DNA by enzymatically or chemically activated mitomycins and porfiromycins, bifunctionally “alkylating” antibiotics. Fed. Proc. 23, 946–957 (1964)Google Scholar
  26. Tarmy, E.M., Venitt, S., Brookes, P.: Mutagenicity of the carcinogen 7-bromomethylbenz(α)anthracene: a quantitative study in repair-deficient strains of Escherichia coli. Mutat. Res. 19, 153–166 (1973)Google Scholar
  27. Tempest, P.R., Moseley, B.E.B.: Role of the gene mtcA in the resistance of Micrococcus radiodurans to the lethal effects of mitomycin C and alkylation mutagenesis. In: DNA repair mechanisms (P.C. Hanawalt, E.C. Friedberg and C.F. Fox, eds.), pp. 283–286. New York: Academic Press 1978Google Scholar
  28. Thielmann, H.W.: Carcinogen-induced DNA repair in nucleotidepermeable Escherichia coli cells. Analysis of DNA repair induced by the carcinogens N-acetoxy-N-2-acetylaminofluorene and 7-bromomethylbenz(α)anthracene. Eur. J. Biochem. 61, 501–513 (1976)Google Scholar
  29. Vielmetter, W., Schuster, H.: The base specificity of mutation induced by nitrous acid in phage T2. Biochem. Biophys. Res. Commun. 2, 324–328 (1960)Google Scholar
  30. Westra, J.G., Kriek, E., Hittenhausen, H.: Identification of the persistently bound form of the carcinogen N-acetyl-2-aminofluorene to rat liver DNA in vivo. Chem.-biol. Interact. 15, 149–164 (1976)Google Scholar
  31. Witkin, E.M.: Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol Rev. 40, 869–907 (1976)Google Scholar
  32. Yamamoto, Y., Sekiguchi, M.: Pathways for repair of DNA damaged by alkylating agent in Escherichia coli. Mol. Gen. Genet. 171, 251–256 (1979)Google Scholar
  33. Yamasaki, H., Pulkrabek, P., Grunberger, D., Weinstein, I.B.: Differential excision from DNA of the C-8 and N2 guanosine adducts of N-acetyl-2-aminofluorene by single strand-specific endonucleases. Cancer Res. 37, 3756–3760 (1977)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Philip R. Tempest
    • 1
  • Bevan E. B. Moseley
    • 1
  1. 1.Department of MicrobiologyUniversity of EdinburghEdinburghScotland

Personalised recommendations