Responses of E. coli to DNA Damage and Stress

  • Toshihiro Ohta
  • John R. Battista
  • Caroline E. Donnelly
  • Graham C. Walker


Exposure of Escherichia coli to agents that damage DNA or interfere with DNA replication results in the induction of the SOS response. A number of chromosomal genes that are repressed by the LexA protein are transcribed at higher levels and various lysogenic bacteriophage are induced. The RecA protein becomes activated by binding to some intracellular inducing signal, probably single-stranded DNA and then mediates proteolytic cleavage of LexA and bacteriophage repressors by facilitating an otherwise latent capacity of these molecules to autodigest. The products of the SOS-regulated operon umuDC axe required for most UV and chemical mutagenesis. We have shown that the UmuD protein shares homology with the carboxyl-terminal domains of LexA and several bacteriophage repressors and is activated for its role in mutagenesis by a RecA-mediated proteolytic event. Thus the regulation of umuD involves a transcriptional derepression and a posttranslational activation that are mechanistically and evolutionary related. A set of missense mutants of umuD was isolated and shown to encode mutant UmuD proteins that are deficient in RecA-mediated cleavage in vivo but which can be partially cleaved at a higher UV dose. Most of these mutations are dominant to umuD* with respect to UV mutagenesis yet do not interfere with SOS induction. Although both UmuD and UmuD’ form homodimers, we have found evidence that they preferentially form heterodimers. These studies of umuD have suggested a role for intact UmuD in the modulation of SOS mutagenesis. Other genetic studies have indicated that the RecA protein plays a third role in mutagenesis besides mediating the cleavage of LexA and UmuD. In addition, we have observed that efficiency of UV mutagenesis is greatly reduced by mutations affecting the groESand groEL heat-shockgenes. These genes encode proteins that function as molecular chaperones which mediate protein folding and protein-protein interaction. It seems possible that they may play a role in the proper assembly of a protein complex required for SOS mutagenesis.


Chemical Mutagenesis LexA Protein Mediate Cleavage Bacteriophage Repressor Transcriptional Derepression 
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.
    Bagg, A., Kenyon, C. J., & Walker, G.C. (1981) Proc. Natl. Acad. Sci. USA 78,5749–5753.PubMedCrossRefGoogle Scholar
  2. 2.
    Bates, H., Randall, S.K., Rayssiguier, C, Bridges, B. A., Goodman, M. F. and Radman, M. (1989) J. Bacteriol. 171, 2480–2484.PubMedGoogle Scholar
  3. 3.
    Battista, J.R., Nohmi, T., Donnelly, C.E. and Walker, G.C. Role of UmuD and UmuC in UV and Chemical Mutagenesis. In: “Mechanisms and Consequences of DNA Damage Processing”, (Eds.) E.C. Friedberg, P.C. Hanawalt, pp455–459, Alan R. Liss, Inc., New York, (1988a).Google Scholar
  4. 4.
    Battista, J.R., Nohmi, T., Donnelly, C.E., and Walker, G.C. (1989) Amino Acid Similarities to Other Proteins Offer Insights Into Roles of UmuD and UmuC In Mutagenesis. Genome 31, 594–596.PubMedGoogle Scholar
  5. 5.
    Battista, J. R., Ohta, T., Nohmi, T., Sun, W., and Walker, G.C. (1990) Proc. Natl. Acad, Sci. USA 87, 7190–7194.CrossRefGoogle Scholar
  6. 6.
    Bonner, C. A., Randall, S. K., Rayssiguier, C., Radman, M., Eritja, R., Kaplan, B.E., McEntee, K. and Goodman, M.R. (1988) J. Biol. Chem. 263, 18946–18952.PubMedGoogle Scholar
  7. 7.
    Bridges, B.A., & Mottershead, R.P. (1978) Mol. Gen. Genet. 162, 35–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Bridges, B. A. & Woodgate, R. (1984) Mol. Gen. Genet. 196 364–366.PubMedCrossRefGoogle Scholar
  9. 9.
    Bridges, B. A. & Woodgate, R. (1985) Proc. Natl. Acad. Sci USA 82, 4193–4197.PubMedCrossRefGoogle Scholar
  10. 10.
    Burckhardt, S. E., Woodgate, R., Scheuermann, R. H., & Echols, H. (1988) Proc. Natl. Acad. Sci. USA 85, 1811–1815.PubMedCrossRefGoogle Scholar
  11. 11.
    Cupido, M.(1983) Mutat. Res. 109, 1–11.Google Scholar
  12. 12.
    Defais, M., Caillet-Fauquet, P., Fox, M. S., & Radman, M. (1976) Mol. Gen. Genet. 148, 125–130.PubMedCrossRefGoogle Scholar
  13. 13.
    Donnelly, C, and Walker, G.C. (1989) J. Bacteriol. 171, 6117–6125.PubMedGoogle Scholar
  14. 14.
    Dutreix, M., Moreau, P. L, Bailone, A., Galibert, F., Battista, J. R., Walker, G. C. and Devoret, R. (1989) J. Bacteriol. 171, 2415–2423.PubMedGoogle Scholar
  15. 15.
    Eguchi, Y., Ogawa, T., & Ogawa, H. (1988) J. Molec. Biol. 202, 565–574.PubMedCrossRefGoogle Scholar
  16. 16.
    Elledge, S.J. & Walker, G.C. (1983) J. Molec. Biol. 164, 175–192.PubMedCrossRefGoogle Scholar
  17. 17.
    Elledge, S.J. & Walker, G.C. (1983) J. Bacteriol. 155, 1306–1315.PubMedGoogle Scholar
  18. 18.
    Ennis, D.G., Ossanna, N., and Mount, D.W. (1989) J. Bacteriol. 171, 2533–2541.PubMedGoogle Scholar
  19. 19.
    Fersht, A. R. & Knill-Jones, J.W. (1983) J. Molec. Biol. 165, 669–682.PubMedCrossRefGoogle Scholar
  20. 20.
    Foster, P.L., Sullivan, A.D., & Franklin, S. B. (1989) J. Bacteriol. 171, 3144–3151.PubMedGoogle Scholar
  21. 21.
    Gimble, F.S., and Sauer, R.T. (1986) J. Molec. Biol. 192, 39–47.PubMedCrossRefGoogle Scholar
  22. 22.
    Gimble, F.S., and Sauer, R.T. (1989) J. Molec. Biol. 206, 29–39.PubMedCrossRefGoogle Scholar
  23. 23.
    Hagensee, M.E., Timme, T., Bryan, S., & Moses, R. (1987) Proc. Natl. Acad. Sci. USA 84, 4149–4199.CrossRefGoogle Scholar
  24. 24.
    Hevroni, D. and Livneh, Z. (1988) J. Biol. Chem. 85, 5046–5050.Google Scholar
  25. 25.
    Hunkapiller, M. W., Smallcombe, S. H., Whitaker, D. R., and Richards, J. H.(1973) Biochemistry 12, 4732.PubMedCrossRefGoogle Scholar
  26. 26.
    Jonczyk, P., Fijalkowska, I., & Ciesla, Z. (1988) Proc. Natl. Acad. Sci. USA 85, 9124–9127.PubMedCrossRefGoogle Scholar
  27. 27.
    Kato, T. & Shinoura, Y. (1977) Mol. Gen. Genet. 156, 121–131.PubMedGoogle Scholar
  28. 28.
    Kitagawa, Y., Akaboshi, E., Shinagawa, H., Horii, T., Ogawa, H. & Kato, T. (1985) Proc. Natl. Acad. Sci. USA 82, 4336–4340.PubMedCrossRefGoogle Scholar
  29. 29.
    Lackey, D., Krauss, S.W., & Linn, S. (1982) Proc. Natl. Acad Sci. USA 79, 330–334.PubMedCrossRefGoogle Scholar
  30. 30.
    Lin, L.-L. & Little, J.W. (1988) J. Bacteriol. 170, 2163–2173.PubMedGoogle Scholar
  31. 31.
    Little, J.W. (1984) Proc. Natl. Acad. Sci. USA 81, 1375–1379.PubMedCrossRefGoogle Scholar
  32. 32.
    Livneh, Z. (1986) J. Biol. Chem. 261, 9526–9533.PubMedGoogle Scholar
  33. 33.
    Lu, C, Scheuermann, H. & Echols, H. (1986) Proc. Natl. Acad. Sci. USA 83, 619–623.PubMedCrossRefGoogle Scholar
  34. 34.
    Mace, D. C. & Alberts, B. M. (1984) J. Molec. Biol. 177, 279–293.PubMedCrossRefGoogle Scholar
  35. 35.
    Marsh, L & Walker, G.C.(1985) J. Bacteriol. 162, 155–161.PubMedGoogle Scholar
  36. 36.
    McCann, J., Choi, E., Yamasaki, E., Ames, B.N. (1975) Proc. Natl. Acad,. Sci. USA 72, 5135–5139.CrossRefGoogle Scholar
  37. 37.
    Miller, (1983) Ann. Rev. Genet. 12, 215–238.CrossRefGoogle Scholar
  38. 38.
    Molina, A. M., Babulri, N., Tamaro, M. Venturini, S. & Monti-Bragadin, C. (1979) FEMS Microbiol. Lett. 5, 33–37.CrossRefGoogle Scholar
  39. 39.
    Nohmi, T., Battista, J. R., Dodson, L. A. and Walker, G.C. (1988) Proc. Natl. Acad. Sci. USA 82,4331–4335.Google Scholar
  40. 40.
    Perry, K. L, Elledge, S. J., Mitchell, B. B., Marsh, L & Walker, G. C. (1985) Proc. Natl. Acad. Sci. 82,4331–4335.PubMedCrossRefGoogle Scholar
  41. 41.
    Perry, K. L. & Walker, G. C. (1982) Nature (London) 300, 278–281.CrossRefGoogle Scholar
  42. 42.
    Radman, M. (1974) In Molec. and Environ. Aspects of Mutagen, edited by L. Prakash, F. Sherman, M. Miller, C. Lawrence, and H. W. Tabor (Springfield, IL., Charles C. Thomas, Pub), 128–142.Google Scholar
  43. 43.
    Sassanfar, M., & Roberts, J. W. (1990) J. Molec. Biol. 212, 79–96.PubMedCrossRefGoogle Scholar
  44. 44.
    Sauer, R. T., Yocum, R. R., Doolittle, R. F., Lewis, M. & Pabo, C. O. (1982) Nature 298, 447–451.PubMedCrossRefGoogle Scholar
  45. 45.
    Sedgwick, S. G. & Goodwin, P. A. (1985) Proc. Natl. Acad. Sci USA 82, 4172–4176.PubMedCrossRefGoogle Scholar
  46. 46.
    Shinagawa, H., Iwasaki, H., Kato, T., & Nakata, A. (1988) Proc. Natl. Acad. Sci. USA 85, 1806–1810.PubMedCrossRefGoogle Scholar
  47. 47.
    Slilaty, S. N. & Little, J. W. (1987) Proc. Natl. Acad. Sci. USA 84, 3987–3991.PubMedCrossRefGoogle Scholar
  48. 48.
    Steinborn, G. (1978) Mol. Gen. Genet. 165, 87–93.PubMedCrossRefGoogle Scholar
  49. 49.
    Strike, P. & Lodwick, D. (1988) J. Cell. Biochem. (Suppl. 12A, 326.Google Scholar
  50. 50.
    Strike, P., & Lodwick, D. (1987) J. Cell. Sci. 10(Suppl. 6), 303–321.Google Scholar
  51. 51.
    Walker, G. C. (1984) Microbiol. Rev. 48, 60–93.PubMedGoogle Scholar
  52. 52.
    Walker, G. C. (1985) Ann. Rev. Biochem. 54, 425–457.PubMedCrossRefGoogle Scholar
  53. 53.
    Weigle, J. J. (1953) Proc. Natl. Acad. Sci. USA 39, 628–636.PubMedCrossRefGoogle Scholar
  54. 54.
    Witkin, E. M. (1969) Ann. Rev. Microbiol. 23, 487–514.CrossRefGoogle Scholar
  55. 55.
    Witkin, E. M. (1975) Mol. Gen. Genet. 142, 87–103.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1992

Authors and Affiliations

  • Toshihiro Ohta
    • 1
  • John R. Battista
    • 1
  • Caroline E. Donnelly
    • 1
  • Graham C. Walker
    • 1
  1. 1.Department of BiologyMassachusetts Institute of TechnologyCambridge

Personalised recommendations