Advertisement

Mechanisms of Spontaneous Mutagenesis: Clues from Altered Mutational Specificity in DNA Repair-Defective Strains

  • Barry W. Glickman
  • Philip A. Burns
  • Douglas F. Fix
Part of the Basic Life Sciences book series (BLSC, volume 39)

Abstract

Spontaneous mutation may be described as the net result of all that can go wrong with DNA during the life cycle of an organism. The student of mutation, however, views the world of mutation through a myriad of filters and sees only a fraction of the molecular events surrounding mutation. To begin with, the student sees only those changes that produce a selectable and hence observable alteration in phenotype. Moreover, the majority of errors made during DNA replication and the errors produced by the accumulation of DNA damage are corrected by the plethora of repair mechanisms that have evolved to maintain the accurate transmission of genetic material. Hence, the study of mutagenesis in strains defective in DNA repair can be expected to yield information about the sources of spontaneous mutation, both with respect to the errors avoided as well as to those errors made during attempts at repair. Our increasing knowledge about mechanisms of DNA repair and their influence on mutation, coupled with the newly developed ability to clone and sequence DNA containing mutations, provides an opportunity to explore the sources of spontaneous mutation.

Keywords

Frameshift Mutation Base Substitution Spontaneous Mutation None None Palindromic Sequence 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Albertini, A.M., M. Hofer, M.P. Calos, and J.H. Miller (1982) On the formation of spontaneous deletions: The importance of short sequence homologies in the generation of large deletions. Cell 29:319–328.CrossRefGoogle Scholar
  2. 2.
    Brychcy, T., and R.C. von Borstel (1977) Spontaneous mutability in U.V.-sensitive excision-defective strains of Saccharomyces. Mutat. Res. 45:185–194.CrossRefGoogle Scholar
  3. 3.
    Calos, M.P., D. Galas, and J.H. Miller (1978) Genetic studies on the lac repressor. VIII, DNA sequence change resulting from an intragenic duplication, J. Mol. Biol. 126:865–869.CrossRefGoogle Scholar
  4. 4.
    Calos, M.P., L. Johnsrud, and J.H. Miller (1978) DNA sequence at the integration sites of the insertion element ISl. Cell 13:411–418.CrossRefGoogle Scholar
  5. 5.
    Calos, M.P., and J.H. Miller (1980) Transposable elements. Cell 20: 579–595.CrossRefGoogle Scholar
  6. 6.
    Calos, M.P., and J.H. Miller (1981) Genetic and sequence analysis of frameshift mutations induced by ICR-191. J. Mol. Biol. 153:39–66.Google Scholar
  7. 7.
    Cheung, S., K. Arndt, and P. Lu (1984) Correlation of lac operator DNA imino protein exchange kinetics with its function. Proc. Natl. Acad. Sci., USA 81:3665–3669.CrossRefGoogle Scholar
  8. 8.
    Coukell, M.B., and C. Yanofsky (1970) Increased frequency of deletions in DNA polymerase mutants of Escherichia coli. Nature (London) 228: 633–636.CrossRefGoogle Scholar
  9. 9.
    Coulondre, C., J.H. Miller, P.J. Farabaugh, and W. Gilbert (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775–780.CrossRefGoogle Scholar
  10. 10.
    DeBoer, J.G., and L.S. Ripley (1984) Demonstration of the production of frameshift and base substitution mutation by quasipalindromic DNA sequences. Proc. Natl. Acad. Sci., USA 81:5528–5531.CrossRefGoogle Scholar
  11. 11.
    DiFrancesco, R., S.K. Bhatnagar, A. Brown, and M.J. Bessman (1984) The interaction of DNA polymerase III and the product of the Escherichia coli mutator gene, mutD. J. Biol. Chem. 259:5567–5573.Google Scholar
  12. 12.
    Drake, J.W. (1969) Comparative rates of spontaneous mutation. Nature 221:1182.CrossRefGoogle Scholar
  13. 13.
    Drake, J.W., E.F. Allen, S.A. Forsberg, R.M. Preparata, and E.O. Greening (1969) Spontaneous mutation: Genetic control of mutation rates in bacteriophage T4. Nature 221:1128–1132.CrossRefGoogle Scholar
  14. 14.
    Drake, J.W., B.W. Glickman, and L.S. Ripley (1983) Updating the theory of mutation. Am. Scientist 71:621–630.Google Scholar
  15. 15.
    Duncan, B.K., and J.H. Miller (1980) Mutagenic deamination of cytosine residues in DNA. Nature 287:560–561.CrossRefGoogle Scholar
  16. 16.
    Duncan, B.K., and B. Weiss (1978) Uracil-DNA glycosylase mutants are mutators. In DNA Repair Mechanisms, P.C. Hanawalt, E.G. Friedberg, and G.F. Fox, eds. Academic Press, Inc., New York, p. 183.Google Scholar
  17. 17.
    Duncan, B.K., and B. Weiss (1982) Specific mutator effect of (ura- cil-DNA-glycosylase) mutations in Escherichia coli. J. Bacteriol. 151:750–755.Google Scholar
  18. 18.
    Echols, H., G. Lu, and P.M.J. Burgers (1983) Mutator strains of Esche-richia coli, mutP and dnaQ, with defective exonucleolytic editing by DNA polymerase III holoenzyme. Proc. Natl. Acad. Sci., USA 80:2189- 2192.Google Scholar
  19. 19.
    Farabaugh, P.J., U. Schmeissner, M. Hofer, and J.H. Miller (1978) Ge-netics studies of the lac repressor. VII. On the molecular nature of spontaneous hotspots in the lad gene of Escherichia coli. J. Mol. Biol. 126:847–863.CrossRefGoogle Scholar
  20. 20.
    Foster, P.L., E. Eisenstadt, and J.H. Miller (1983) Base substitution mutations induced by metabolically activated aflatoxin Bl. Proc. Natl. Acad. Sci., USA 80:2695–2698.CrossRefGoogle Scholar
  21. 21.
    Fowler, R.G., R.M. Schaaper, and B.W. Glickman (1986) The role of 3“ 5” exonuclease (proofreading activity) in DNA replication fidelity: A characterization of mutational specificity within the lad gene for a mutD5 mutator strain of Escherichia coli. J. Bacteriol. (in press).Google Scholar
  22. 22.
    Fridovich, I. (1976) Oxygen radicals, hydrogen peroxide, and oxygen toxicity. In Free Radicals in Biology, Vol. 1, W.A. Pryor, ed. Aca-demic Press, Inc., New York, pp. 239–277.Google Scholar
  23. 23.
    Galas, D.J., M.P. Galos, and J.H. Miller (1980) Sequence analysis of Tn9 insertions in the lacZ gene. J. Mol. Biol. 144:19–41.CrossRefGoogle Scholar
  24. 24.
    Glickman, B.W. (1979) Spontaneous mutagenesis in Escherichia coli strains lacking N6-methyladenine residues in their DNA. Mutat. Res. 61:153–159.CrossRefGoogle Scholar
  25. 25.
    Glickman, B.W., and M. Radman (1980) Escherichia coli mutator defi-cient in methylation-instructed DNA mismatch correction. Proc. Natl. Acad. Sci., USA 77:1063–1067.CrossRefGoogle Scholar
  26. 26.
    Glickman, B.W., and L.S. Ripley (1984) Structural intermediates of deletion mutagenesis: A role for palindromic DNA. Proc. Natl. Acad. Sci., USA 81:512–516.CrossRefGoogle Scholar
  27. 27.
    Gomez-Eichelmann, M.C., and K.G. Lark (1977) Endo R Dpn I restriction Escherichia coli DNA synthesized vitro. Evidence that the ends of Okazaki pieces are determined by template deoxyribonucleotide se-quence. J. Mol. Biol. 117:621–635.CrossRefGoogle Scholar
  28. 28.
    Hastings, P.J., S.K. Quah, and R.C. von Borstel (1976) Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA. Nature 264:719–722.CrossRefGoogle Scholar
  29. 29.
    Johnsrud, L. (1979) DNA sequence of the transposable element Isl. Mol. Gen. Genet. 169:213–218.CrossRefGoogle Scholar
  30. 30.
    Kern, R., and F.K. Zimmermann (1978) The influence of defects in exci-sion and error prone repair on spontaneous and induced mitotic recom-bination and mutation in Saccharomyces eerevisiae. Mol. Gen. Genet. 161:81–88.CrossRefGoogle Scholar
  31. 31.
    Kleekner, N. (1981) Transposable elements in prokaryotes. Ann. Rev. Genet. 15:391–404.Google Scholar
  32. 32.
    Kondo, S., H. Ichikawa, K. Iwo, and T. Kato (1970) Base change mutagenesis and prophage induction in strains of Escherichia coli with different DNA repair capacities. Genetics 66:187–217.Google Scholar
  33. 33.
    Konrad, E.B. (1978) Isolation of an Escherichia coli K-12 dnaE mutation as a mutator. J. Bacteriol. 133:1197–1202.Google Scholar
  34. 34.
    Romberg, A. (1980) DNA Replication, W.H. Freeman and Company, San Francisco.Google Scholar
  35. 35.
    Kuhn, S., H.J. Fritz, and P. Starlinger (1979) Close vicinity of ISj. integration sites in the leader sequence of the gal operon of E. coli. Mol. Gen. Genet. 167:235–242.CrossRefGoogle Scholar
  36. 36.
    Kunkel, T.A. (1984) The mutational specificity of depurination. Proc. Natl. Acad. Sci., USA 81:1494–1498.CrossRefGoogle Scholar
  37. 37.
    Kunz, B.A., and B.W. Glickman (1984) The role of pyrimidine dimers as premutagenic lesions: A study of targeted vs. untargeted mutagenesis in the lad gene of Escherichia coli. Genetics 106:347–364.Google Scholar
  38. 38.
    Lindahl, T. (1979) DNA-glycosylases-endonucleases for apurinic/apyri- midic sites and base excision-repair. Prog. Nucl. Acid Res. Mol. Biol. 22:135–191.CrossRefGoogle Scholar
  39. 39.
    Loeb, L.A., and T.A. Kunkel (1982) Fidelity of DNA synthesis. Ann. Rev. Biochem. 51:429–457.CrossRefGoogle Scholar
  40. 40.
    Lu, A.L., K. Welsh, S. Clark, S.S. Su, and P. Modrich (1984) Repair of DNA basepair mismatches in extracts of Escherichia coli. Cold Spring Harbor Sywp. Quant. Biol. 49:589–596.CrossRefGoogle Scholar
  41. 41.
    Macquat, L., K. Thornton, and W. Reznikoff (1980) lac promoter mutations located downstream from the transcription start site. J. Mol. Biol. 139:537–549.CrossRefGoogle Scholar
  42. 42.
    Miller, J.H. (1983) Mutational specificity in bacteria. Ann. Rev. Genet. 17:215–239.CrossRefGoogle Scholar
  43. 43.
    Muller, H.J., and L.M. Mott-Smith (1930) Evidence that natural radioactivity is inadequate to explain the frequency of “natural” mutations. Proc. Natl. Acad. Sci., USA 16:277–285.CrossRefGoogle Scholar
  44. 44.
    Okada, Y., G. Streisinger, J. Owen, J. Newton, A. Tsugita, and M. Inouye (1972) Molecular basis of a mutational hotspot in the lysozyme gene of bacteriophage T4. Nature 263:338–341.CrossRefGoogle Scholar
  45. 45.
    Pribnow, D., D.C. Sigurdson, L. Gold, B.S. Singer, J. Brosius, T.J. Dull, and M.F. Noller (1981) rll cistrons of bacteriophage T4: DNA sequence around the intercistronic divide and positions of genetic landmarks. J. Mol. Biol. 149:337–376.CrossRefGoogle Scholar
  46. 46.
    Ripley, L.S. (1982) Model for the participation of quasipalindromic DNA sequences in frameshift mutation, Proc. Natl. Acad. Sci., USA 79:4128–4132.CrossRefGoogle Scholar
  47. 47.
    Ripley, L.S., and B.W. Glickman (1984) DNA secondary structure and mutation in cellular responses to DNA damage. In UCLA Symposia on Molecular and Cellular Biology. A New Series, E.C. Friedberg and B.A. Bridges, eds. Alan Liss, Inc., New York, pp. 521–540.Google Scholar
  48. 48.
    Ripley, L.S., and B.W. Glickman (1983) Unique self-complementarity of palindromic sequences provides DNA structural intermediates for mutation. Cold Spring Harbor Symp, Quant. Biol. 47:851–861.CrossRefGoogle Scholar
  49. 49.
    Ripley, L.S., and N.B. Shoemaker (1983) A major role for bacteriophage T4 DNA polymerase in frameshift mutagenesis. Genetics 103:353–366.Google Scholar
  50. 50.
    Sargentini, N.J., and K.C. Smith (1981) Much spontaneous mutagenesis in Escherichia coli is due to error-prone DNA repair. Carcinogenesis 2:863–872.CrossRefGoogle Scholar
  51. 51.
    Sargentini, N.J., and K.C. Smith (1985) Spontaneous mutagenesis: The roles of DNA repair, replication, and recombination. Mutat. Res. 154:1–27.Google Scholar
  52. 52.
    Savic, D.J., and S.P. Roinac (1982) Powerful mutator activity of the polAl mutation within the histidine region of Escherichia coli K-12. J. Bacteriol. 149:955–960.Google Scholar
  53. 53.
    Schaaper, R.M., B.N. Danforth, and B.W. Glickman (1985) Rapid repeated cloning of mutant lac repressor genes. Gene 39:181–189.CrossRefGoogle Scholar
  54. 54.
    Schaaper, R.M., B.N. Danforth, and B.W. Glickman (1986) Mechanisms of spontaneous mutagenesis: An analysis of spectrum of spontaneous muta-tion in the E. coli lad gene. J. Mol. Biol, (in press).Google Scholar
  55. 55.
    Schaaper, R.M., T.A. Kunkel, and L.A. Loeb (1983) Infidelity of DNA synthesis associated with bypass of apurinic sites. Proc. Natl. Acad. Sci., USA 80:487–491.CrossRefGoogle Scholar
  56. 56.
    Scheuermann, R., S. Tam, P.M.J. Burgers, C. Lu, and H. Echols (1983) Identification of the E-subunit of Escherichia coli DNA polymerase III holoenzyme as the dnaQ gene product: A fidelity subunit for DNA rep-lication. Proc. Natl. Acad. Sci., USA 80:7085–7089.CrossRefGoogle Scholar
  57. 57.
    Siegel, E.G., and K.K. Vaccaro (1978) The reversion of frameshift mutations in mut, polA, lig, and dnaE mutant strains of Escherichia coli. Mutat. Res. 50:9–17.CrossRefGoogle Scholar
  58. 58.
    Speyer, J.F., J.D. Karam, and A.B. Lenny (1966) On the role of DNA polymerase in base selection. Gold Spring Harbor Symp. Quant. Biol. 31:693–697.CrossRefGoogle Scholar
  59. 59.
    Streisinger, G., Y. Okada, J. Emrich, J. Newton, A. Tsugita, E. Terzaghi, and M. Inouye (1966) Frameshift mutations and the genetic code. Cold Spring Harbor Symp. Quant. Biol. 33:77–84.CrossRefGoogle Scholar
  60. 60.
    Todd, P.A., and B.W. Glickman (1982) Mutational specificity of UV- light in Escherichia coli: Indications for a role of DNA secondary structure. Proc. Natl. Acad. Sci., USA 79:4123–4127.CrossRefGoogle Scholar
  61. 61.
    Topal, M.D., and J.R. Fresco (1976) Complementary base pairing and the origin of substitution mutations. Nature 263:285–289.CrossRefGoogle Scholar
  62. 62.
    Vaccaro, K.K., and E.G. Seigel (1975) Increased spontaneous reversion of certain frameshift mutations in DNA polymerase I deficient strains of Escherichia coli. Mol. Gen. Genet. 141:251–262.CrossRefGoogle Scholar
  63. 63.
    von Borstel, R.C. (1969) On the origin of spontaneous mutations. Japan. J. Genet. 44:102–105.Google Scholar
  64. 64.
    Warner, H.R., B.K. Duncan, C. Garett, and J. Neuhard (1981) Synthesis and metabolism of uracil-containing deoxyribonucleic acid in Escher-ichia coli. J. Bacteriol. 145:687–695.Google Scholar
  65. 65.
    Watson, J.D., and F.H.C. Crick (1953) The structure of DNA. Cold Spring Harbor S3mip. Quant. Biol. 18:123–131.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Barry W. Glickman
    • 1
  • Philip A. Burns
    • 1
  • Douglas F. Fix
    • 1
  1. 1.Department of BiologyYork UniversityDownsviewCanada

Personalised recommendations