Skip to main content
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1983 Jan;153(1):33–44. doi: 10.1128/jb.153.1.33-44.1983

Mutagenesis, by methylating and ethylating agents, in mutH, mutL, mutS, and uvrD mutants of Salmonella typhimurium LT2.

W G Shanabruch, R P Rein, I Behlau, G C Walker
PMCID: PMC217339  PMID: 6401281

Abstract

Salmonella typhimurium LT2 mutH, mutL, mutS, and uvrD mutants were especially sensitive to mutagenesis by both the recA+-dependent mutagen methyl methane sulfonate and the recA+-independent mutagen ethyl methane sulfonate, but not to mutagenesis by agents such as 4-nitroquinoline-1-oxide and UV irradiation. Similarly, these mutator strains were very sensitive to mutagenesis by the methylating agents N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea. The increased susceptibility to mutagenesis by small alkylating agents due to mutH, mutL, mutS, and uvrD mutations was not accompanied by an increased sensitivity to killing by these agents. Various models are discussed in an effort to explain why strains thought to be deficient in methyl-instructed mismatch repair are sensitive to mutagenesis by methylating and ethylating agents.

Full text

PDF
37

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott P. J., Saffhill R. DNA synthesis with methylated poly(dC-dG) templates. Evidence for a competitive nature to miscoding by O(6)-methylguanine. Biochim Biophys Acta. 1979 Mar 28;562(1):51–61. doi: 10.1016/0005-2787(79)90125-4. [DOI] [PubMed] [Google Scholar]
  2. Ames B. N., Lee F. D., Durston W. E. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Natl Acad Sci U S A. 1973 Mar;70(3):782–786. doi: 10.1073/pnas.70.3.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  4. Bachmann B. J., Low K. B. Linkage map of Escherichia coli K-12, edition 6. Microbiol Rev. 1980 Mar;44(1):1–56. doi: 10.1128/mr.44.1.1-56.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Campbell A., Berg D. E., Botstein D., Lederberg E. M., Novick R. P., Starlinger P., Szybalski W. Nomenclature of transposable elements in prokaryotes. Gene. 1979 Mar;5(3):197–206. doi: 10.1016/0378-1119(79)90078-7. [DOI] [PubMed] [Google Scholar]
  6. Cox E. C. Bacterial mutator genes and the control of spontaneous mutation. Annu Rev Genet. 1976;10:135–156. doi: 10.1146/annurev.ge.10.120176.001031. [DOI] [PubMed] [Google Scholar]
  7. Geier G. E., Modrich P. Recognition sequence of the dam methylase of Escherichia coli K12 and mode of cleavage of Dpn I endonuclease. J Biol Chem. 1979 Feb 25;254(4):1408–1413. [PubMed] [Google Scholar]
  8. Glickman B. W., Radman M. Escherichia coli mutator mutants deficient in methylation-instructed DNA mismatch correction. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1063–1067. doi: 10.1073/pnas.77.2.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Glickman B., van den Elsen P., Radman M. Induced mutagenesis in dam- mutants of Escherichia coli: a role for 6-methyladenine residues in mutation avoidance. Mol Gen Genet. 1978 Jul 25;163(3):307–312. doi: 10.1007/BF00271960. [DOI] [PubMed] [Google Scholar]
  10. Gómez-Eichelmann M. C. Deoxyribonucleic acid adenine and cytosine methylation in Salmonella typhimurium and Salmonella typhi. J Bacteriol. 1979 Nov;140(2):574–579. doi: 10.1128/jb.140.2.574-579.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ishii Y., Kondo S. Comparative analysis of deletion and base-change mutabilities of Escherichia coli B strains differing in DNA repair capacity (wild-type, uvrA-, polA-, recA-) by various mutagens. Mutat Res. 1975 Jan;27(1):27–44. doi: 10.1016/0027-5107(75)90271-7. [DOI] [PubMed] [Google Scholar]
  12. Karran P., Lindahl T., Griffin B. Adaptive response to alkylating agents involves alteration in situ of O6-methylguanine residues in DNA. Nature. 1979 Jul 5;280(5717):76–77. doi: 10.1038/280076a0. [DOI] [PubMed] [Google Scholar]
  13. Karran P., Marinus M. G. Mismatch correction at O6-methylguanine residues in E. coli DNA. Nature. 1982 Apr 29;296(5860):868–869. doi: 10.1038/296868a0. [DOI] [PubMed] [Google Scholar]
  14. Kato T., Shinoura Y. Isolation and characterization of mutants of Escherichia coli deficient in induction of mutations by ultraviolet light. Mol Gen Genet. 1977 Nov 14;156(2):121–131. doi: 10.1007/BF00283484. [DOI] [PubMed] [Google Scholar]
  15. 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. 1970 Oct;66(2):187–217. doi: 10.1093/genetics/66.2.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lacks S., Greenberg B. Complementary specificity of restriction endonucleases of Diplococcus pneumoniae with respect to DNA methylation. J Mol Biol. 1977 Jul;114(1):153–168. doi: 10.1016/0022-2836(77)90289-3. [DOI] [PubMed] [Google Scholar]
  17. Lawley P. D., Martin C. N. Molecular mechanisms in alkylation mutagenesis. Induced reversion of bacteriophage T4rII AP72 by ethyl methanesulphonate in relation to extent and mode of ethylation of purines in bacteriophage deoxyribonucleic acid. Biochem J. 1975 Jan;145(1):85–91. doi: 10.1042/bj1450085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marinus M. G., Morris N. R. Isolation of deoxyribonucleic acid methylase mutants of Escherichia coli K-12. J Bacteriol. 1973 Jun;114(3):1143–1150. doi: 10.1128/jb.114.3.1143-1150.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McCann J., Spingarn N. E., Kobori J., Ames B. N. Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. Proc Natl Acad Sci U S A. 1975 Mar;72(3):979–983. doi: 10.1073/pnas.72.3.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mortelmans K. E., Stocker B. A. Segregation of the mutator property of plasmid R46 from its ultraviolet-protecting property. Mol Gen Genet. 1979 Jan 2;167(3):317–327. doi: 10.1007/BF00267425. [DOI] [PubMed] [Google Scholar]
  21. Mortelmans K. E., Stocker B. A. Ultraviolet light protection, enhancement of ultraviolet light mutagenesis, and mutator effect of plasmid R46 in Salmonella typhimurium. J Bacteriol. 1976 Oct;128(1):271–282. doi: 10.1128/jb.128.1.271-282.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nevers P., Spatz H. C. Escherichia coli mutants uvr D and uvr E deficient in gene conversion of lambda-heteroduplexes. Mol Gen Genet. 1975 Aug 27;139(3):233–243. doi: 10.1007/BF00268974. [DOI] [PubMed] [Google Scholar]
  23. Olsson M., Lindahl T. Repair of alkylated DNA in Escherichia coli. Methyl group transfer from O6-methylguanine to a protein cysteine residue. J Biol Chem. 1980 Nov 25;255(22):10569–10571. [PubMed] [Google Scholar]
  24. Radding C. M. Genetic recombination: strand transfer and mismatch repair. Annu Rev Biochem. 1978;47:847–880. doi: 10.1146/annurev.bi.47.070178.004215. [DOI] [PubMed] [Google Scholar]
  25. Radman M., Villani G., Boiteux S., Kinsella A. R., Glickman B. W., Spadari S. Replicational fidelity: mechanisms of mutation avoidance and mutation fixation. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):937–946. doi: 10.1101/sqb.1979.043.01.103. [DOI] [PubMed] [Google Scholar]
  26. Rydberg B. Bromouracil mutagenesis and mismatch repair in mutator strains of Escherichia coli. Mutat Res. 1978 Oct;52(1):11–24. doi: 10.1016/0027-5107(78)90091-x. [DOI] [PubMed] [Google Scholar]
  27. Sanderson K. E., Hartman P. E. Linkage map of Salmonella typhimurium, edition V. Microbiol Rev. 1978 Jun;42(2):471–519. doi: 10.1128/mr.42.2.471-519.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schaaper R. M., Loeb L. A. Depurination causes mutations in SOS-induced cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1773–1777. doi: 10.1073/pnas.78.3.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schendel P. F., Robins P. E. Repair of O6-methylguanine in adapted Escherichia coli. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6017–6020. doi: 10.1073/pnas.75.12.6017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Seeberg E. Reconstitution of an Escherichia coli repair endonuclease activity from the separated uvrA+ and uvrB+/uvrC+ gene products. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2569–2573. doi: 10.1073/pnas.75.6.2569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shanabruch W. G., Behlau I., Walker G. C. Spontaneous mutators of salmonella typhimurium LT2 generated by insertion of transposable elements. J Bacteriol. 1981 Sep;147(3):827–835. doi: 10.1128/jb.147.3.827-835.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Siegel E. C. Ultraviolet-sensitive mutator strain of Escherichia coli K-12. J Bacteriol. 1973 Jan;113(1):145–160. doi: 10.1128/jb.113.1.145-160.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Siegel E. C., Wain S. L., Meltzer S. F., Binion M. L., Steinberg J. L. Mutator mutations in Escherichia coli induced by the insertion of phage mu and the transposable resistance elements Tn5 and Tn10. Mutat Res. 1982 Mar;93(1):25–33. doi: 10.1016/0027-5107(82)90122-1. [DOI] [PubMed] [Google Scholar]
  34. Sinzinis B. I., Smirnov G. B., Saenko A. A. Repair deficiency in Escherichia coli UV-sensitive mutator strain uvr502. Biochem Biophys Res Commun. 1973 Jul 2;53(1):309–316. doi: 10.1016/0006-291x(73)91435-6. [DOI] [PubMed] [Google Scholar]
  35. Sklar R., Strauss B. Role of the uvrE gene product and of inducible O6-methylguanine removal in the induction of mutations by N-methyl-N'-nitro-N-nitrosoguanidine in Escherichia coli. J Mol Biol. 1980 Nov 15;143(4):343–362. doi: 10.1016/0022-2836(80)90217-x. [DOI] [PubMed] [Google Scholar]
  36. Tiraby J. G., Fox M. S. Marker discrimination in transformation and mutation of pneumococcus. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3541–3545. doi: 10.1073/pnas.70.12.3541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Todd P. A., Brouwer J., Glickman B. W. Influence of DNA-repair deficiencies on MMS- and EMS-induced mutagenesis in Escherichia coli K-12. Mutat Res. 1981 Jul;82(2):239–250. doi: 10.1016/0027-5107(81)90153-6. [DOI] [PubMed] [Google Scholar]
  38. Wagner R., Jr, Meselson M. Repair tracts in mismatched DNA heteroduplexes. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4135–4139. doi: 10.1073/pnas.73.11.4135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Walker G. C., Dobson P. P. Mutagenesis and repair deficiencies of Escherichia coli umuC mutants are suppressed by the plasmid pKM101. Mol Gen Genet. 1979 Apr 17;172(1):17–24. doi: 10.1007/BF00276210. [DOI] [PubMed] [Google Scholar]
  40. Walker G. C. Plasmid (pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in Escherichia coli K-12. Mol Gen Genet. 1977 Mar 28;152(1):93–103. doi: 10.1007/BF00264945. [DOI] [PubMed] [Google Scholar]
  41. White R. L., Fox M. S. On the molecular basis of high negative interference. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1544–1548. doi: 10.1073/pnas.71.4.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wildenberg J., Meselson M. Mismatch repair in heteroduplex DNA. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2202–2206. doi: 10.1073/pnas.72.6.2202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Witkin E. M. Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol Rev. 1976 Dec;40(4):869–907. doi: 10.1128/br.40.4.869-907.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Witkin E. M., Wermundsen I. E. Targeted and untargeted mutagenesis by various inducers of SOS functions in Escherichia coli. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):881–886. doi: 10.1101/sqb.1979.043.01.095. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES