Regulation and Function of Cellular Gene Products Involved in UV and Chemical Mutagenesis in E. Coli

  • Graham C. Walker
  • Stephen J. Elledge
  • Karen L. Perry
  • Anne Bagg
  • Cynthia J. Kenyon
Part of the Basic Life Sciences book series (volume 15)


The past few years have seen a remarkable increase in our understanding of the strategies employed by cells in dealing with damage to their genetic material. Of particular interest has been the recognition that mutagenesis by a variety of agents including UV, methyl methanesulfonate (MMS), and 4-nitroquinoline-1-oxide (NQO) is not a passive process. Rather it requires the intervention of a cellular system which processes damaged DNA in such a way that mutations result. Mutagenesis is not a necessary consequence of DNA damage since, if this system is inactivated, no mutations result. In this paper we would like to summarize some of the recent work of our lab on the cellular molecular mechanisms involved in UV and chemical mutagenesis.


Chemical Mutagenesis Spontaneous Mutation Rate lexA Protein Apurinic Site Phage Survival 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Witkin, E.M.: Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol. Rev., 40: 869 (1976)PubMedGoogle Scholar
  2. 2.
    Weigle, J.J.: Induction of mutations in a bacterial virus. Proc. Nat.Acad. Sci. U.S.A., 39: 628 (1953)CrossRefGoogle Scholar
  3. 3.
    Defais, M., Fauquet, P., Radman, M., Errera, M.: Ultraviolet reactivation and ultraviolet mutagenesis of λ in different genetic systems. Virology, 43: 495 (1971)PubMedCrossRefGoogle Scholar
  4. 4.
    Radman, M.: SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis. In Molecular Mechanisms for Repair of DNA, Ed. by P.C. Hanawalt, and R.B. Setlow. Plenum Publishing Corp, New York, part A, p. 355 (1978)Google Scholar
  5. 5.
    Kato, T., Shinoura, Y.: Isolation and characterization of mutants of Escherichia coli deficient in induction of mutations by ultraviolet light. Molec. Gen. Genet., 156: 121 (1977)PubMedGoogle Scholar
  6. 6.
    Steinborn, G.: Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. Molec. Gen. Gene, 165: 87 (1978)PubMedCrossRefGoogle Scholar
  7. 7.
    Boiteux, S., Villani, G., Spadari, S., Zambrano, F., Redman, M.: Making and correcting errors in DNA synthesis: in vitro studies of mutagenesis. In DNA Repair Mechanisms, Ed. by P.C. Hanawalt, E.C. Friedberg, C.F. Fox. Academic Press New York, p. 73 (1978)Google Scholar
  8. 8.
    Villani, G., Boiteux, S., Radman, M.: Mechanisms of ultraviolet—induced mutagenesis: extent and fidelity of in vitro DNA synthesis on irradiated templates. Proc. Natl. AcadSci. U.S.A., 75: 3037 (1978)PubMedCrossRefGoogle Scholar
  9. 9.
    Walker, G.C., Dobson, P.P.: Mutagenesis and repair deficiencies of Escherichia coli umuC mutants are suppressed by the plasmid pKM101. Molec. Gen. Genet., 172: 17 (1979)PubMedCrossRefGoogle Scholar
  10. 10.
    Steinborn, G. Uvm Mutants of Escherichia coli K12 Deficient in UV Mutagenesis. Molec. Gen. Genet., 175: 203 (1979)CrossRefGoogle Scholar
  11. 11.
    Casadaban, M.J. and Cohen, S.N.: Lactose genes fused to exogenous promoters in one step using a Mu—lac bacteriophage: In vivo probe for transcriptional control. Proc. Natl. Acad. Sci. U.S.A., 76: 4530 (1979)PubMedCrossRefGoogle Scholar
  12. 12.
    Bagg, A., Kenyon, C.J. and Walker, G.C.: Inducibility of a gene product required for UV and chemical mutagenesis in Escherichia coll. Proc. Natl. Acad. Sci. U.S.A., in press (1981)Google Scholar
  13. 13.
    Little, J.W., Harper, J.E.: Identification of the lexA gene product of Escherichia coli K-12. Proc. Nat. Acad. Sci. U.S.A., 76: 6147 (1979)CrossRefGoogle Scholar
  14. 14.
    Kenyon, C.J. and Walker, G.C.: DNA-damaging agents stimulate gene expression at specific loci in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A., 77: 2819 (1980)PubMedCrossRefGoogle Scholar
  15. 15.
    Kenyon, C.J. and Walker, G.C.: Expression of the uvrA gene of Escherichia coli is inducible. Nature, 289: 810 (1981)CrossRefGoogle Scholar
  16. 16.
    Fogliano, M. and Schendel, P.F.: Evidence for the inducibility of the uvrB operon. Nature, 289: 196 (1981)PubMedCrossRefGoogle Scholar
  17. 17.
    Huisman, 0. and D’Ari, R.: An inducible DNA replication-cell division coupling mechanism in Escherichia coli. Nature, 290: 797 (1981)CrossRefGoogle Scholar
  18. 18.
    McEntee, K., Hesse, J.E. and Epstein, W.: Identification and radiochemical purification of the recA protein of Escherichia coli. Proc. Natl. Acad. Sci. U.S.A., 73: 3979 (1976)PubMedCrossRefGoogle Scholar
  19. 19.
    Brent, R. and Ptashne, M.: The lexA gene product represses its own promoter. Proc. Natl. Acad. Sci. U.S.A., 77: 1932 (1977)CrossRefGoogle Scholar
  20. 20.
    Walker, G.C., Kenyon, C.J., Bagg, A., Langer, P.J. and Shanabruch, W.G.: Mutagenesis and cellular responses to DNA damage. J. Nat. Cancer Institute Monograph, in press (1981)Google Scholar
  21. 21.
    Walker, G.C., Kenyon, C.J., Bagg, A., Elledge, S.J., Perry, K.L. and Shanabruch, W.G.: Regulation and functions of Escherichia coli genes induced by DNA damage. In Molecular and Cellular Mechanisms of Mutagenesis, Ed. by J.F. Lemontt and W.M. Generoso. Plenum Press, New York, in press (1981)Google Scholar
  22. 22.
    Schendel, P.F. and Defais, M.: The role of the umuC gene product in mutagenesis by simple alkylating agents. Molec. Gen. Genet., 177: 661 (1980)PubMedCrossRefGoogle Scholar
  23. 23.
    Coulondre, C. and Miller, J.H.: Genetic studies of the lac repressor IV. J. Molec. Bio., 117: 577 (1977)PubMedCrossRefGoogle Scholar
  24. 24.
    Olsson, M. and Lindahl, T.: Repair of alkylated DNA in Escherichia coli: methyl group transfer from 0 6-methylguanine to a protein cysteine residue. J. Biol. Chem., 255: 10569 (1980)PubMedGoogle Scholar
  25. 25.
    Eisenstadt, E., Wolf, M. and Goldberg, I.H.: Mutagenesis by neocarcinostatin in Escherichia coli and Salmonella typhimurium: requirement for umuC or plasmid pKMl01. J. Bacteriol., 144: 656 (1980)PubMedGoogle Scholar
  26. 26.
    McCann, J., Choi, E., Yamasaki, E. and Ames, B.N.: Detection of carcinogens as mutagens in the Salmonella/-microsome test: assay of 300 chemicals. Proc. Natl. Acad. Sci. U.S.A., 72: 5135 (1975)PubMedCrossRefGoogle Scholar
  27. 27.
    Glickman, B.W. and Radman, M.: Escherichia coli mutators deficient in methylation-instructed mismatch repair correction. Proc. Natl. Acad. Sci. U.S.A., 77: 1063 (1980)PubMedCrossRefGoogle Scholar
  28. 28.
    Radman, M., Wagner, R.E., Glickman, B.W. and Meselson, M.: DNA methylation, mismatch correction and genetic stability. In Progress in Environmental Mutagenesis, Ed. by M. Alecevic. Elsevier/North Holland Biomedical Press, Amsterdam, p. 121 (1980)Google Scholar
  29. 29.
    George, T., Castellazzi, M. and Butlin, G.: Prophage induction and cell division in E. coli III. Mutations sfiA and sfiB restore division in tif and lon strains and permit the expression of mutator properties of tif. Molec. Gen. Genet., 140: 309 (1975)Google Scholar
  30. 30.
    Witkin, E.M.: Thermal enhancement of ultraviolet mutability in a tif-1 uvrA derivative of Escherichia coli B/r: evidence that ultraviolet mutagenesis depends upon an inducible function. Proc. Natl. Acad. Sci. U.S.A., 71: 1930 (1974)PubMedCrossRefGoogle Scholar
  31. 31.
    Drabble, W.T. and Stocker, B.A.D.: R (transmissible drug-resistance) factors in S. typhimurium: pattern of transduction by phage P22 and ultraviolet protection effect. J. Gen. Microbiol., 53: 109 (1968)PubMedGoogle Scholar
  32. 32.
    Mortelmans, K.E. and Stocker, B.A.D.: Ultraviolet light protection, enhancement of ultraviolet light mutagenesis, and mutator effect of plasmid R46 in Salmonella typhimurium. J. Bacteriol., 128: 271 (1976)PubMedGoogle Scholar
  33. 33.
    Mortelmans, K. and Stocker, B.A.D.: Segregation of the mutator property of plasmid R46 from its ultraviolet-protecting property. Molec. Gen. Genet. 167: 317 (1979)PubMedCrossRefGoogle Scholar
  34. 34.
    Langer, P.J. and Walker, G.C.: Restriction endonuclease cleavage map of pKM101: relationship to parental plasmid R46. Molec. Gen. Genet., in press (1981)Google Scholar
  35. 35.
    Langer, P.J., Shanabruch, W.G. and Walker, G.C.: Functional organization of the plasmid pKM101. J. Bacteriol., 145: 1310 (1981)PubMedGoogle Scholar
  36. 36.
    McCann, J., Spingarn, N.E., Kobori, J. and Ames, B.N.: Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. Proc. Natl. Acad. Sci. U.S.A., 72: 979 (1975)PubMedCrossRefGoogle Scholar
  37. 37.
    McCann, J. and Ames, B.N.: Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc. Natl. Acad. Sci. U.S.A., 73: 950 (1976)PubMedCrossRefGoogle Scholar
  38. 38.
    Walker, G.C.: Theory and design of short term bacterial tests for mutagenesis. In Assessing Chemical Mutagens: the Risk to Humans, Ed. by V.K. McElheny and S. Abrahamson. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, p. 63 (1979).Google Scholar
  39. 39.
    Walker, G.C.: Molecular principles underlying the Ames Salmonella/microsome test: elements and design of short term mutagenesis test. Ed. by A.R. Kolber and T.K. Wang. Plenum Press, New York, in press (1981)Google Scholar
  40. 40.
    Walker, G.C.: Plasmid(pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in Escherichia coli K-12. Molec. Gen. Genet., 152: 93 (1977)PubMedCrossRefGoogle Scholar
  41. 41.
    Goze, A. and Devoret, R.: Repair promoted by plasmid pKM101 is different from SOS repair. Mutat. Res., 61: 163 (1979)PubMedCrossRefGoogle Scholar
  42. 42.
    Shanabruch, W.G. and Walker, G.C.: Localization of the plasmid (pKM101) gene(s) involved in recA+lexA+-dependent mutagenesis. Molec. Gen. Genet., 179: 289 (1980)PubMedCrossRefGoogle Scholar
  43. 43.
    Walker, G.C.: Isolation and characterization of mutants of the plasmid pKM101 deficient in their ability to enhance mutagenesis and repair. J. Bacteriol., 133: 1203 (1978b)PubMedGoogle Scholar
  44. 44.
    Walker, G.C.: Inducible reactivation and mutagenesis of UV-irradiated bacteriophage P22 in Salmonella typhimurium LT2 containing the plasmid pKM101. J. Bacteriol., 135: 415 (1978a)PubMedGoogle Scholar
  45. 45.
    Dobson, P.P. and Walker, G.C.: Plasmid (pKM101)-mediated Weigle reactivation in Escherichia coli K-12 and Salmonella typhimurium LT2: Genetic dependence, kinetics of induction, and effect of chloramphenicol. Mutat. Res., 71: 25 (1980)PubMedCrossRefGoogle Scholar
  46. 46.
    Casadaban, M.J., Chou, J. and Cohen, S.N.: In vitro gene fusions that join an enzymatically active ß-galactosidase segment to amino-terminal fragments of exogenous proteins: Escherichia coli plasmid vectors for the detection and cloning of translation initiation signals, J. Bacterial., 143: 971 (1980)Google Scholar
  47. 47.
    Kato, T. and Nakano, E.: The effects of the umuC36 mutation on ultraviolet-induced base changes and frameshift mutations in Escherichia coli. Mutat. Res., in press (1981)Google Scholar
  48. 48.
    Ichikawa-Rho, H. and Kondo, S.: Indirect mutagenesis in phage lambda by ultraviolet preirradiation of host bacteria. J. Molec. Biol., 97: 77 (1975)CrossRefGoogle Scholar
  49. 49.
    Caillet-Fauquet, P., Defais, M. and Radman, M.: Molecular mechanisms of induced mutagenesis: Replication in vivo of bacteriophage MX174 single-stranded, ultraviolet light-irradiated DNA in intact and irradiated host cells. J. Molec. Biol., 117: 95 (1977)PubMedCrossRefGoogle Scholar
  50. 50.
    Lippke, J.A., Gordon, L.K., Brash, D.E. and Haseltine, W.A.: The distribution of ultraviolet light induced damage in a defined sequence of human DNA: Detection of alkaline sensitive lesions at pyrimidine-cytosine sequences. Proc. Natl. Acad. Sci. U.S.A., in press (1981)Google Scholar
  51. 51.
    Schaaper, R.M. and Loeb, L.A.: Depurination causes mutations in SOS-induced cells. Proc. Natl. Acad. Sci. U.S.A., 78: 1773 (1981)PubMedCrossRefGoogle Scholar
  52. 52.
    Bridges, B.A., Mottershead, R.P. and Sedgwick, S.G.: Mutagenic DNA repair in Escherichia coli III. Requirement for a function of DNA polymerase III in Eultraviolet light mutagenesis. Molec. Gen. Genet., 144: 53 (1976)PubMedCrossRefGoogle Scholar
  53. 53.
    Fields, P.I. and Yasbin, R.E.: Involvement of deoxyribonucleic acid polymerase III in W-reactivation in Bacillus subtilis. J. Bacteriol., 144: 473 (1980)PubMedGoogle Scholar
  54. 54.
    Cooper, P.K. and Hanawalt, P.C.: Role of DNA polymerase I and the rec system in excision repair in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A., 69: 1156 (1972)PubMedCrossRefGoogle Scholar
  55. 55.
    Kato, T.: Effects of chloramphenicol and caffeine on postreplication repair in uvrA umuC and uvrA recF strains of Escherichia coli. Molec. Gen. Genet., 156: 115–120 (1977)PubMedGoogle Scholar
  56. 56.
    Sanderson, K.E. and Hartman, P.E.: Linkage map of Salmonella typhimurium. edition V., Microbiol. Rev., 42: 471 (1978)Google Scholar
  57. 57.
    Kimball, R.F., Boling, M.E., and Perdue, S.W.: Evidence that UV-inducible error-prone repair is absent in Haemophilus influenzaeRd., with a discussion of the relation to error-prone repair of alkylating-agent damage. Mutat. Res., 44: 183 (1977)PubMedCrossRefGoogle Scholar
  58. 58.
    Notani, N.K. and Setlow, J.E.: Inducible repair system in Haemophilus influenzae unaccompanied by mutation. J. Bacteriol., 143: 516 (1980)PubMedGoogle Scholar
  59. 59.
    Hollstein, M., McCann, J., Angelosanto, F.A. and Nichols, W.W.: Short term tests for carcinogens and mutagens. Mutat. Res., 65: 133 (1979)PubMedGoogle Scholar
  60. 60.
    Moreau, P., Bailone, A. and Devoret, R.: Prophage X induction in Escherichia coli K12 envA uvrB: A highly sensitive test for potential carcinogens. Proc. Natl. Acad. Sci. U.S.A., 73: 3700 (1976)PubMedCrossRefGoogle Scholar
  61. 61.
    Speck, W., Santella, R.M. and Rosenkranz, H.S.: An evaluation of the prophage λ (Inductest) for the detection of potential carcinogens. Mutat. Res., 54: 101 (1978)PubMedGoogle Scholar
  62. 62.
    Samson, L. and Cairns, J.: A new pathway for DNA repair in Escherichia coli. Nature, 267: 281 (1977)CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Graham C. Walker
    • 1
  • Stephen J. Elledge
    • 1
  • Karen L. Perry
    • 1
  • Anne Bagg
    • 1
  • Cynthia J. Kenyon
    • 1
  1. 1.Biology DepartmentMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations