Skip to main content

Part of the book series: Basic Life Sciences ((BLSC,volume 31))

Summary

Experimental evidence indicates that while thymine starvation induces primarily A:T → G:C transitions in bacteria, it also may cause other uncharacterized base substitutions as well as frame-shifts and deletions. However, models have been proposed to explain only the induction of point mutations by thymine deprivation. In this study, we demonstrate that thymine nucleotide depletion induces both point mutations in the his-4 and lacI genes of Escherichia coli and reversion of the frameshift mutations trpE9777, trpA21, trpA540, and trpA9813. Analysis of the 1acI amber spectrum revealed that thymine starvation resulted in G:C → A:T transitions and all possible transversions. A defect in uracil-DNA glycosylase has little effect on the induction of lacl - mutations but reduces substantially the induction of trpE9777 revertants. These data show that the mutagenic specificity of thymine nucleotide depletion is not limited to A:T → G:C transitions and suggest that removal of uracil from DNA plays a role in the generation of frameshift mutations by thymine deprivation. A model that involves nucleotide misincorporation into DNA and induction of error-prone repair functions in response to thymine starvation is proposed to account for these findings.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. L. E. Bertani, A, Haggmark, and P. Reichard, Enzymatic synthesis of deoxyribonucleotides. II. Formation and interconver- sion of deoxyuridine phosphates, J. Biol. Chem., 238: 3407–3413 (1963).

    PubMed  CAS  Google Scholar 

  2. J. L. Bousque and N. Sicard, Size and transforming activity of deoxyribonucleic acid in Diplococcus pneumoniaduring thymine starvation, J. Bacteriol., 128: 540–548 (1976).

    PubMed  CAS  Google Scholar 

  3. T. R. Breitman, P. B. Maury, and J. N. Toal, Loss of deoxyribonucleic acid-thymine during thymine starvation of Escherichia coli, J. Bacteriol., 112: 646–648 (1972).

    PubMed  CAS  Google Scholar 

  4. S. E. Bresler, M. I. Mosevitsky, andL. Vyacheslavov, Complete mutagenesis in a bacterial population induced by thymine starvation on solid media, Nature, 225: 764–766 (1970).

    Article  PubMed  CAS  Google Scholar 

  5. S. Bresler, M. Mosevitsky, and L. Vyacheslavov, Mutations as possible replication errors in bacteria growing under conditions of thymine deficiency, Mutat. Res., 19: 281–293 (1973).

    Article  PubMed  CAS  Google Scholar 

  6. B. A. Bridges, J. Law, and R. J. Munson, Mutagenesis in Escherichia coli. II. Evidence for a common pathway for mutagenesis by ultraviolet light, ionizing radiation and thymine deprivation, Molec. Gen. Genet., 103: 266–273 (1968).

    Article  PubMed  CAS  Google Scholar 

  7. F. Brunei, A. M. Sicard, and N. Sicard, Transformaing activity of bacterial deoxyribonucleic acid in relation to marker efficiencies in Diplococcus pneumoniae during thymine starvation, J. Bacteriol., 106: 904–907 (1971).

    Google Scholar 

  8. R. N. Buick and W. J. Harris, Thymineless death in Bacillus subtilis, J. Gen. Microbiol., 88: 115–122 (1975).

    PubMed  CAS  Google Scholar 

  9. M. P. Calos and J. H. Miller, Genetic and sequence analysis of frameshift mutations induced by ICR-191, J. Molec. Biol., 153: 39–66 (1981).

    Article  PubMed  CAS  Google Scholar 

  10. S. S. Cohen and H. D. Barner, Studies on unbalanced growth in Escherichia coli, Proc. Natl. Acad. Sci. U.S.A., 40: 885–893 (1954).

    Article  PubMed  CAS  Google Scholar 

  11. C. A. Coughlin and E. A. Adelberg, Bacterial mutation induced by thymine starvation, Nature, 178: 531–532 (1956).

    Article  PubMed  CAS  Google Scholar 

  12. C. Coulondre and J. H. Miller, Genetic studies of the lac repressor. III. Additional correlation of mutational sites with specific amino acid residues, J. Molec. Biol., 117: 525–575 (1977).

    Article  PubMed  CAS  Google Scholar 

  13. C. Coulondre and J. H. Miller, Genetic studies of the lacrepressor. IV. Mutagenic specificity in the lacl gene of Escherichia coli, J. Molec. Biol., 117: 577–606 (1977).

    Article  PubMed  CAS  Google Scholar 

  14. C. Coulondre, J. H. Miller, P. J. Farabaugh, and W. Gilbert, Molecular basis of base substitution hotspots in Escherichia coli, Nature, 274: 775–780 (1978).

    Article  PubMed  CAS  Google Scholar 

  15. H. DeBarjac, Thymine-requiring mutants of the insect pathogen Bacillus thuringiensis, J. Invert. Pathol., 16: 321–324 (1970).

    Article  CAS  Google Scholar 

  16. C. E. Deutch and C. Pauling, Thyminelss mutagenesis in Escherichia coli, J. Bacteriol., 119: 861–867 (1974).

    PubMed  CAS  Google Scholar 

  17. W. A. Deutsch and A. L. Spiering, A new pathway expressed during a distinct stage of Drosophiladevelopment for the removal of dUMP residues in DNA, J. Biol. Chem., 257: 3366–3368 (1982).

    PubMed  CAS  Google Scholar 

  18. B. K. Duncan and J. H. Miller, Mutagenic deamination of cytosine residues in DNA, Nature, 287: 560–561 (1980).

    Article  PubMed  CAS  Google Scholar 

  19. B. K. Duncan, P. A. Rockstroh, and H. R. Warner, Escherichia coliK12 mutants deficient in uracil-DNA glycosylase, J. Bacteriol., 134: 1039–1045 (1978).

    PubMed  CAS  Google Scholar 

  20. B. K. Duncan and B. Weiss, in: “DNA Repair Mechanisms” (P. C. Hanawalt, E. C. Friedberg, and C. F. Fox, eds.), pp. 183–186, Academic Press, Inc., New York (1978).

    Google Scholar 

  21. B. K. Duncan and B. Weiss, Specific mutator effects of ung (uracil-DNA glycosylase) mutations in Escherichia coli, J. Bacteriol., 151: 750–755 (1982).

    PubMed  CAS  Google Scholar 

  22. P. J. Farabaugh, Sequence of the laclgene, Nature, 274: 765–769 (1978).

    Article  PubMed  CAS  Google Scholar 

  23. P. J. Farabaugh, U. Schmeissner, M. Hofer, and J. H. Miller, Genetic studies of the lacrepressor. VII. On the molecular nature of spontaneous hotspots in the laclgene of Escherichia coli, J. Molec. Biol., 126: 847 - 863 (1978).

    Article  PubMed  CAS  Google Scholar 

  24. J. L. Farmer and F. Rothman, Transformable thymine-requiring mutant of Bacillus subtilis, J. Bacteriol., 89: 262–263 (1964).

    Google Scholar 

  25. D. Freifelder, Single strand breaks in bacterial DNA associated with thymine starvation, J. Molec. Biol., 45: 1–7 (1969).

    Article  PubMed  CAS  Google Scholar 

  26. S. M. Frisch, J. L. Couch, and D. A. Glaser, Mutator activity of a short Okazaki fragment mutant of Escherichia coli, J. Bacteriol., 134: 1192–1194 (1978).

    PubMed  CAS  Google Scholar 

  27. J. Gallant and T. Spottswood, Measurement of the stability of the repressor of alkaline phosphatase synthesis in Escherichia coli, Proc. Natl. Acad. Sci., U.S.A., 52: 1591–1598 (1964).

    Article  PubMed  CAS  Google Scholar 

  28. J. Gallant and S. R. Suskind, Relation between thymineless death and ultraviolet inactivation in Escherichia coli, J. Bacteriol., 82: 187–194 (1961).

    PubMed  CAS  Google Scholar 

  29. A. M. Gasc, N. Sicard, J. P. Claverys, and A. M. Sicard, Lack of SOS repair in Streptococcus pneumoniae, Mutat. Res., 70: 157–165 (1980).

    Article  PubMed  CAS  Google Scholar 

  30. F. T. Gates and S. Linn, Endonuclease V of Escherichia coli, J. Biol. Chem., 252: 1647–1653 (1977).

    PubMed  CAS  Google Scholar 

  31. C. S. Genther, R. S. Schoeny, J. C. Loper, and C. C. Smith, Mutagenic studies of folic acid antagonists, Antimicrob. Agents Chemother., 12: 84–92 (1977).

    PubMed  CAS  Google Scholar 

  32. B. W. Glickman, Spontaneous mutagenesis in Escherichia colistrains lacking 6-methyladenine residues in their DNA. An altered mutational spectrum in dam- mutants, Mutat. Res., 61: 153–162 (1979).

    Article  PubMed  CAS  Google Scholar 

  33. M. Goulian and W. Beck, Variations of intracellular deoxyribosyl compounds in deficiencies of vitamin B12, folic acid, and thymine, Biochim. Biophys. Acta, 129: 336–349 (1966).

    CAS  Google Scholar 

  34. L. J. Gudas and A. B. Pardee, DNA synthesis inhibition and the induction of protein X in Escherichia coli, J. Molec. Biol., 101: 459–477 (1976).

    Article  PubMed  CAS  Google Scholar 

  35. W. E. Hill and W. L. Fangman, Single-strand breaks in deoxyribonucleic acid and viability loss during deoxyribonucleic acid synthesis inhibition in Escherichia coli, J. Bacteriol., 116: 1329–1335 (1973).

    PubMed  CAS  Google Scholar 

  36. A. J. Holmes and A. Eisenstark, The mutagenic effect of thymine starvation on Salmonella typhimurium, Mutat. Res., 5: 15–21 (1968).

    Article  PubMed  CAS  Google Scholar 

  37. D. Kanazir, The apparent mutagenicity of thymine deficiency, Biochim. Biophys. Acta, 30: 20–23 (1958).

    Article  PubMed  CAS  Google Scholar 

  38. T. Kato and E. Nakano, Effects of the umuC36mutation on ultraviolet-radiation-induced base-change and frameshift mutations in Escherichia coli, Mutat. Res., 83: 307–319 (1981).

    Article  PubMed  CAS  Google Scholar 

  39. T. Kato, Y. Shinoura, A. Templin, and A. J. Clark, Analysis of ultraviolet light-induced suppressor mutations in the strain of Escherichia coliK12 AB1157: an implication for molecular mechanisms of mutagenesis, Molec. Gen. Genet., 180: 283–291 (1980).

    Article  PubMed  CAS  Google Scholar 

  40. D. Korn and A. Weissbach, Thymineless induction in Escherichia coliK12 (λ), Biochim. Biophys. Acta, 61: 775–790 (1962).

    PubMed  CAS  Google Scholar 

  41. B. A. Kunz and B. W. Glickman, The infidelity of conjugal DNA replication in Escherichia coli, Genetics, 105: 489–500 (1983).

    PubMed  CAS  Google Scholar 

  42. T. Lindahl, An N-glycosidase from Escherichia colithat releases free uracil from DNA containing deaminated cytosine residues, Proc. Natl. Acad. Sci., U.S.A., 71: 3649–3653 (1974).

    Article  PubMed  CAS  Google Scholar 

  43. T. Lindahl, DNA glycosylases, endonucleases for apurinic/apyrimidinic sites, and base excision repair, Progr. Nucl. Acid Res. Molec. Biol., 22: 135–191 (1979).

    Article  CAS  Google Scholar 

  44. J. G. Little and P. C. Hanawalt, Thymineless death and ultraviolet sensitivity in Micrococcus radiodurans, J. Bacteriol., 113: 233–240 (1973).

    PubMed  CAS  Google Scholar 

  45. F. Makino and N. Munakata, Deoxyuridine residues in DNA of thymine-requiring Bacillus subtilisstrains with defective N-glycosidase activity for uracil-containing DNA, J. Bacteriol., 134: 24–29 (1978).

    PubMed  CAS  Google Scholar 

  46. L. G. Mathieu, J. DeRepentigny, J. Turgeon, and S. Sonea, Thymineless death of Staphylococcus aureusand formation of its alpha toxin, Can. J. Microbiol., 14: 983–987 (1968).

    Article  PubMed  CAS  Google Scholar 

  47. J. H. Miller, Experiments in Molecular Genetics, Cold Spring Harbor Laboratory, Cold Spring Harbor (1972).

    Google Scholar 

  48. J. H. Miller, C. Coulondre, and P. J. Farabaugh, Correlation of nonsense sites in the laclgene with specific codons in the nucleotide sequence, Nature, 274: 770–775 (1978).

    Article  PubMed  CAS  Google Scholar 

  49. J. H. Miller, D. Ganem, P. Lu, and A. Schmitz, Genetic studies of the lacrepressor. I. Correlation of mutational sites with specific amino acid residues: construction of a co-linear gene-protein map, J. Molec. Biol., 109: 275–301 (1977).

    Article  PubMed  CAS  Google Scholar 

  50. J. H. Miller and U. Schmeissner, Genetic studies of the lacrepressor. X. Analysis of missense mutations in the laclgene, J. Molec. Biol., 131: 223–248 (1979).

    Article  PubMed  CAS  Google Scholar 

  51. P. Mukopadhyay and S. Palchaudhuri, Trimethoprim-produced F- specific insertion mutations in Escherichia coliK12, J. Bacteriol., 150: 755–761 (1975).

    Google Scholar 

  52. H. Nakayama and P. C. Hanawalt, Sedimentation analysis of deoxy ribonucleic acid from thymine-starved Escherichia coli, J. Bacteriol., 121: 537–547 (1975).

    PubMed  CAS  Google Scholar 

  53. J. Neuhard and A. Munch-Peterson, Studies on the acid soluble nucleotide pool in thymine requiring mutants of Escherichia coliduring thymine starvation. II. Changes in the amounts of deoxycytidine triphosphate and deoxyadenosine triphosphate in Escherichia coliT-A-U-, Biochim. Biophys. Acta, 114: 61–71 (1966).

    PubMed  CAS  Google Scholar 

  54. A. J. Norin and E. P. Goldschmidt, Effect of mutagens, chema- therapeutic agents and defects in DNA repair genes on recombination in F’ partial diploid Escherichia coli, Mutat. Res., 59: 15–26 (1979).

    Article  PubMed  CAS  Google Scholar 

  55. C. Pauling, in: “Structural Chemistry and Molecular Biology” (A. Rick and N. Davidson, eds.), pp. 393–398, W. H. Freeman Co., San Francisco (1968).

    Google Scholar 

  56. C. Pauling and P. C. Hanawalt, Non-conservative DNA replication in bacteria after thymine starvation, Proc. Natl. Acad. Sci., U.S.A., 54:1728–1735 (1965).

    Article  PubMed  CAS  Google Scholar 

  57. M. Radman, in: “Molecular and Environmental Aspects of Mutagenesis” (L. Prakash, F. Sherman, M. W. Miller, C. W. Lawrence, and H. W. Taber, eds.), pp. 128–142, Charles C. Thomas, Publisher, Springfield (1974).

    Google Scholar 

  58. G. Ramareddy and H. Reiter, Sequential loss of loci in thymine- starved Bacillus subtilis168 cells: evidence for a circular chromosome, J. Molec. Biol., 50: 525–532 (1970).

    Article  PubMed  CAS  Google Scholar 

  59. J. Reich and J. Soska, Thymineless death and deoxyribonucleotideless death in Lactobacillus acidophilisR-26, Biochem. Biophys. Res. Commun., 29: 62–67 (1967).

    Article  PubMed  CAS  Google Scholar 

  60. D. L. Reichenbach, G. E. Schaiberger, and B. Sallman, The effect of thymine starvation on the chromosomal structure of Escherichia coliJG-151, Biochem. Biophys. Res. Commun., 42: 23–30 (1971).

    Article  PubMed  CAS  Google Scholar 

  61. H. Reiter and G. Ramareddy, The loss of DNA behind the growing point of thymine-starved Bacillus subtilis168, J. Molec. Biol. 50: 533–548 (1970).

    Article  PubMed  CAS  Google Scholar 

  62. R. M. Schaaper, T. A. Kunkel, and L. A. Loeb, Infidelity of DNA synthesis associated with bypass of apurinic sites, Proc. Natl. Acad. Sci., U.S.A., 80: 487–491 (1983).

    Article  PubMed  CAS  Google Scholar 

  63. U. Schmeissner, D. Ganem, and J. H. Miller, Genetic studies of the lacrepressor. II. Fine structure deletion map of the laclgene, and its correlation with the physical map, J. Molec. Biol., 109: 303–326 (1977).

    Article  PubMed  CAS  Google Scholar 

  64. E. C. Siegel and K. K. Vaccaro, The reversion of trpframeshift mutations in mut, polA, lig, and dnaEmutant strains of Escherichia coli, Mutat. Res., 50: 9–17 (1978).

    Article  CAS  Google Scholar 

  65. F. Tamanoi and T. Okazaki, Uracil incorporation into the nascent DNA of thymine-requiring mutant of Bacillus subtilis168, Proc. Natl. Acad. Sci., U.S.A., 75: 2195–2199 (1978).

    Article  PubMed  CAS  Google Scholar 

  66. B.-K. Tye, J. Chien, I. R. Lehman, B. K. Duncan, and H. Warner, Uracil incorporation as a source of pulse-labelled DNA fragments in the replication of the Escherichia colichromosome, Proc. Natl. Acad. Sci., U.S.A., 75: 233–237 (1978).

    Article  PubMed  CAS  Google Scholar 

  67. J. T. Wachsman, S. Kemp, and L. Hogg, Thyminelss death in Bacillus megaterium, J. Bacteriol., 87: 1079–1086 (1964).

    PubMed  CAS  Google Scholar 

  68. J. R. Walker, Thymine starvation and single strand breaks in chromosomal deoxyribonucleic acid of Escherichia coli, 104: 1391–1392 (1970).

    CAS  Google Scholar 

  69. H. R. Warner, B. K. Duncan, C. Garett, and J. Neuhard, Synthe¬sis and metabolism of uracil-containing deoxyribonucleic acid in Escherichia coli, J. Bacteriol., 145: 687–695 (1981).

    PubMed  CAS  Google Scholar 

  70. R. Weinberg and A. B. Latham, Apparent mutagenic effect of thymine deficiency for a thymine-requiring strain of Escherichia coli, J. Bacteriol., 72: 570–572 (1956).

    PubMed  CAS  Google Scholar 

  71. E. M. Witkin, Ultraviolet mutagenesis and inducible repair in Escherichia coli, Bacteriol. Rev., 40: 869–907 (1976).

    PubMed  CAS  Google Scholar 

  72. E. M. Witkin and I. E. Wermundsen, Targeted and untargeted mutagenesis by various inducers of SOS functions in Escherichia coli, Cold Spring Harbor Symp. Quant. Biol., 43: 881–886 (1978).

    Article  Google Scholar 

  73. K. Yoshinaga, Double strand scission of DNA involved in thymineless death of Escherichia coli15 TUA, Biochim. Biophys. Acta, 294: 204–213 (1973).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Plenum Press, New York

About this chapter

Cite this chapter

Kunz, B.A. (1985). Thymineless Mutagenesis in Bacteria. In: de Serres, F.J. (eds) Genetic Consequences of Nucleotide Pool Imbalance. Basic Life Sciences, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2449-2_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-2449-2_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9488-7

  • Online ISBN: 978-1-4613-2449-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics