Situation-Dependent Repair of DNA Damage in Yeast

  • R. C. von Borstel
  • P. J. Hastings
Part of the Basic Life Sciences book series


The concept of channelling of lesions in DNA into defined repair systems has been used to explain many aspects of induced and spontaneous mutation. The channelling hypothesis states that lesions excluded from one repair process will be taken up by another repair process. This is a simplification. The three known modes of repair of damage induced by radiation are not equivalent modes of repair; they are, instead, different solutions to the problem of replacement of damaged molecules with new molecules which have the same informational content as those that were damaged. The mode of repair that is used is the result of the response to the situation in which the damage takes place. Thus, when the most likely mode of repair does not take place, then the situation changes with respect to the repair of the lesion; the lesion may enter the replication fork and be reparable by another route.


Ultraviolet Radiation Excision Repair Repair System Mutation Induction Pyrimidine Dimer 
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. Abbondandolo, A., and Simi, S., 1971, Mosaicism and lethal sectoring in G1 cells of Schizosaccharomyces pombe, Mutat. Res., 12:143–150.PubMedCrossRefGoogle Scholar
  2. Ashwood-Smith, M. J., Poulton, G. A., Barker, M., and Mildenburger, M., 1980, 5-Methoxypsoralen, an ingredient in several suntan preparations, has lethal, mutagenic and clastogenic properties, Nature, 285:407–409.PubMedCrossRefGoogle Scholar
  3. Auerbach, C., 1967, Lethal sectoring and the origin of complete mutants in Schizosaccharomyces pombe, Mutat. Res., 4:875–878.PubMedCrossRefGoogle Scholar
  4. Brash, D. E., and Haseltine, W. A., 1982, UV-induced mutation hot-spots occur at DNA damage hotspots, Nature, 298:189–192.PubMedCrossRefGoogle Scholar
  5. Brendel, M., and Haynes, R. H., 1973, Interaction among genes controlling sensitivity to radiation and alkylation in yeast, Molec. Gen. Genet., 125:197–216.PubMedCrossRefGoogle Scholar
  6. Brychcy, T., 1974, Spontaneous mutability in strains of Saccharomyces cerevisiae sensitive to ultraviolet radiation, M.Sc. Thesis, University of Alberta, 144 pages.Google Scholar
  7. Brychcy, T., and von Borstel, R. C., 1977, Spontaneous mutability in UV-sensitive excision-defective strains of Saccharomyces, Mutat. Res., 45:185–194.PubMedCrossRefGoogle Scholar
  8. Cassier, C., Chanet, R., Henriques, J.-A. P., and Moustacchi, E., 1980, The effects of three pso genes on induced mutagenesis: A novel class of mutationally defective yeast, Genetics, 96:841–857.PubMedGoogle Scholar
  9. Chanet, R., Cassier, C., Magaña-Schwenke, N., and Moustacchi, E., 1983, Fate of photo-induced 8-methoxypsoralen monoadducts in yeast. Evidence for bypass of these lesions in the absence of excision repair, Mutat. Res., 112:201–214.PubMedGoogle Scholar
  10. Cole, R. S., 1971, Inactivation of Escherichia coli, F’ episomes at transfer, and bacteriophage lambda by psoralen plus 360 nm light: Significance of deoxyribonucleic acid cross-links, J. Bacteriol., 107:846–852.PubMedGoogle Scholar
  11. Cole, R. S., Levitan, D., and Sinden, R. R., 1976, Removal of psoralen interstrand cross-links from DNA of Escherlehia colli Mechanism and genetic control, J. Mol. Blol., 103:39–59.CrossRefGoogle Scholar
  12. Conkling, M. A., and Drake, J. W., 1984, Isolation and characterization of conditional alleles of bacteriophage T4 genes uvsX and uvsY, Genetics, 107:505–523.PubMedGoogle Scholar
  13. Cox, B., and Game, J., 1974, Repair systems in Saccharomyces, Mutat. Res., 26:257–264.PubMedCrossRefGoogle Scholar
  14. Dall’Acqua, F., Marciani, S., Ciavatti, L., and Rodighiero, G., 1971, Formation of inter-strand cross-linkings in the photo-reactions between furocoumarins and DNA, Z. Naturforsch., 26B:561–569.Google Scholar
  15. Devoret, R., 1965, Influence du genotype de la bacterie hôte sur la mutation du phage X produite par le rayonnement ultraviolet, C. R. Acad. Sci., 260:1510–1513.Google Scholar
  16. di Caprio, L., and Cox, B. S., 1979, DNA synthesis in UV-irradiated yeast, Mutat. Res., 82:69–85.Google Scholar
  17. Doudney, C. O., and Young, C. S., 1962, Ultraviolet light induced mutation and deoxyribonucleic acid replication in bacteria, Genetics, 47:1125–1138.PubMedGoogle Scholar
  18. Eckardt, R., and Haynes, R. H., 1977a, Induction of pure and sectored mutant clones in excision proficient and deficient strains of yeast, Mutat. Res., 43:327–338.PubMedCrossRefGoogle Scholar
  19. Eckardt, F., and Haynes, R. H., 1977b, Kinetics of mutation induction by ultraviolet light in excision-deficient yeast, Genetics, 85:225–247.PubMedGoogle Scholar
  20. Eckardt, F., and Haynes, R. H., 1980, Quantitative measures of mutagenicity and mutability based on mutant yield data, Mutat. Res., 74:439–458.PubMedGoogle Scholar
  21. Eckardt, F., Teh, S. J., and Haynes, R. H., 1980, Heteroduplex repair as an intermediate step of mutagenesis in yeast, Genetics, 95:63–80.PubMedGoogle Scholar
  22. Franklin, W. A., Lo, K. M., and Haseltine, W. A., 1982, Alkaline lability of novel fluorescent photoproducts produced in ultraviolet light irradiated DNA, J. Biol. Chem., 257:13535–13543.PubMedGoogle Scholar
  23. Game, J. C., 1983, Radiation-sensitive mutants and repair in yeast, in: “Yeast Genetics: Fundamental and Applied Aspects,” J. F. T. Spencer, D. M. Spencer, and A. R. W. Smith, eds., Springer-Verlag, New York, Berlin, Heidelberg, and Tokyo, pp. 109–137.Google Scholar
  24. Game, J. C., and Cox, B. S., 1972, Epistatic interactions between four rad loci in yeast, Mutat. Res., 16:353–362.PubMedCrossRefGoogle Scholar
  25. Game, J. C., and Cox, B. S., 1973, Synergistic interactions between rad mutations in yeast, Mutat. Res., 20:35–44.PubMedCrossRefGoogle Scholar
  26. Game, J. C., Johnston, L. H., and von Borstel, R. C., 1979, Enhanced mitotic recombination in a ligase-defective mutant of the yeast Saccharomyces cerevisiae, Proc. Natl. Acad. Sci. USA, 76:4589–4592.PubMedCrossRefGoogle Scholar
  27. Goodman, H. M., Olson, M. V., and Hall, B. D., 1977, Nucleotide sequence of a mutant eukaryotic gene: The yeast tyrosine-inserting ochre suppressor SUP4-o, Proc. Natl. Acad. Sci. USA, 74:5453–5457.PubMedCrossRefGoogle Scholar
  28. Grant, E. L., von Borstel, R. C., and Ashwood-Smith, M. J., 1979, Mutagenicity of cross-links and monoadducts of furocoumarins (psoralen and angelicin) induced by 360 nm radiation in excision-repair-defective and radiation-insensitive strains of Saccharomyces cerevisiae, Environ. Mutagen., 1:55–63.PubMedCrossRefGoogle Scholar
  29. Hannan, M. A., Duck, P., and Nasim, A., 1976, UV-induced lethal sectoring and pure mutant clones in yeast, Mutat. Res., 36:171–176.PubMedCrossRefGoogle Scholar
  30. Haseltine, W. A., 1983, Ultraviolet light repair and mutagenesis revisited, Cell, 33:13–17.PubMedCrossRefGoogle Scholar
  31. Hastings, P. J., Quah, S-K., and von Borstel, R. C., 1976, Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA, Nature, 264:719–722.PubMedCrossRefGoogle Scholar
  32. Haynes, R. H., and Eckardt, F., 1979, Analysis of dose response patterns in mutation research, Can. J. Genet. Cytol., 21:277–302.PubMedGoogle Scholar
  33. Haynes, R. H., and Kunz, B. A., 1981, DNA repair and mutagenesis in yeast, in: “The Molecular Biology of the Yeast Saccharomyces,” J. N. Strathern, E. W. Jones, and J. R. Broach, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 371–414.Google Scholar
  34. Henriques, J.-A. P., and Moustacchi, E., 1980, Isolation and characterization of pso mutants sensitive to photo-addition of psoralen derivatives in Saccharomyces cerevisiae, Genetics, 95:273–288.PubMedGoogle Scholar
  35. Henriques, J.-A. P., and Moustacchi, E., 1981, Interactions between mutations for sensitivity to psoralen photoaddition (pso) and to radiation (rad) in Saccharomyces cerevisiae, J. Bacteriol., 148:248–256.PubMedGoogle Scholar
  36. Ichikawa-Ryo, H., and Kondo, S., 1975, Indirect mutagenesis in phage lambda by ultraviolet pre-irradiation of host bacteria, J. Mol. Biol., 97:77–92.PubMedCrossRefGoogle Scholar
  37. Igali, S., and von Borstel, R. C., 1974, Evidence for misrepair mutagenesis in Saccharomyces cerevisiae, Book of Abstracts, Fifth International Congress of Radiation Research, Seattle, Washington, 14-20 July 1974, B-15-2, p. 99.Google Scholar
  38. Jachymczyk, W. J., von Borstel, R. C., Mowat, M. R. A., and Hastings, P. J., 1981, Repair of interstrand cross-links in DNA of Saccharomyces cerevisiae requires two systems for repair: The RAD3 system and the RAD51 system, Molec. Gen. Genet., 182:196–205.PubMedCrossRefGoogle Scholar
  39. Jacob, F., 1954, Mutation d’un bacteriophage induite par l’irradiation des seules bacteries-hôtes avant l’infection, C. R. Acad. Sci., 238:732–734.Google Scholar
  40. James, A, P., and Kilbey, B. J., 1977, The timing of UV mutagenesis in yeast: A pedigree analysis of induced recessive mutation, Genetics, 87:237–248.PubMedGoogle Scholar
  41. James, A. P., Kilbey, B. J., and Prefontaine, G., 1978, The timing of UV mutagenesis in yeast. Continuing mutation in an excision defective (rad1-1) strain, Molec. Gen. Genet., 165:207–212.PubMedCrossRefGoogle Scholar
  42. Kilbey, B. J., and James, A. P., 1979, The mutagenic potential of unexcised pyrimidine dimers in Saccharomyces cerevisiae rad1-1. Evidence from photoreactivation and pedigree analysis, Mutat. Res., 60:163–171.PubMedCrossRefGoogle Scholar
  43. Kilbey, B. J., Brychcy, T., and Nasim, A., 1978, Initiation of UV mutagenesis in Saccharomyces cerevisiae, Nature, 274:889–891.CrossRefGoogle Scholar
  44. Kunz, B. A., and Glickman, B. W., 1984, The role of pyrimidine dimers as premutagenic lesions: A study of targeted vs. untargeted mutagenesis in the lacI gene of Escherichia coli, Genetics, 106:347–364.PubMedGoogle Scholar
  45. Lawrence, C. W., and Christensen, R. B., 1982, The mechanism of untargeted mutagenesis in UV-irradiated yeast, Molec. Gen. Genet., 186:1–9.PubMedCrossRefGoogle Scholar
  46. Lemontt, J. F., 1971, Mutants of yeast defective in mutation induced by ultraviolet light, Genetics, 68:21–33.PubMedGoogle Scholar
  47. Lippke, J. A., Gordon, L. K., Brash, D. E., and Haseltine, W. A., 1981, Distribution of UV light-induced damage in a defined sequence of human DNA: Detection of alkaline-sensitive lesions at pyrimidine nucleoside-cytidine sequences, Proc. Natl. Acad. Sci. USA, 78:3388–3392.PubMedCrossRefGoogle Scholar
  48. Little, J. W., and Mount, D. W., 1982, The SOS regulatory system of Escherichia coli, Cell, 29:11–22.PubMedCrossRefGoogle Scholar
  49. Magana-Schwenke, N., Henriques, J.-A. P., Chanet, R., and Moustacchi, E., 1982, The fate of 8-methoxypsoralen photoinduced crosslinks in nuclear and mitochondrial yeast DNA: Comparison of wild-type and repair-deficient strains, Proc. Natl. Acad. Sci. USA, 79:1722–1726.CrossRefGoogle Scholar
  50. Moustacchi, E., 1969, Cytoplasmic and nuclear genetic events induced by UV light in strains of Saccharomyces cerevisiae with different sensitivities, Mutat. Res., 7:171–185.PubMedCrossRefGoogle Scholar
  51. Muhammed, A., 1966, Studies on the yeast photoreactivating enzyme. I. A method for the large scale purification and some properties of the enzyme, J. Mol. Chem., 241:516–523.Google Scholar
  52. Nasim, A., and Auerbach, C., 1967, The origin of complete and mosaic mutants from mutagenic treatment of single cells, Mutat. Res., 4:1–4.PubMedCrossRefGoogle Scholar
  53. Prakash, L., 1976, Effect of genes controlling radiation sensitivity on chemically induced mutations in Saccharomyces cerevisiae, Genetics, 83:285–301.PubMedGoogle Scholar
  54. Prakash, L., and Prakash, S., 1977, Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae, Genetics, 86:33–55.PubMedGoogle Scholar
  55. Prakash, L., and Prakash, S., 1980, Genetic analysis of error prone repair systems, in: “DNA Repair and Mutagenesis in Eukaryotes,” W. M. Generoso, M. D. Shelby, and F. J. de Serres, eds., Plenum Press, New York, pp. 141–158.Google Scholar
  56. Quah, S.-K., von Borstel, R. C., and Hastings, P. J., 1980, The origin of spontaneous mutation in Saccharomyces cerevisiae, Genetics, 96:819–839.PubMedGoogle Scholar
  57. Radman, M., 1974, Phenomenology of an inducible mutagenic DNA repair pathway in Escherichia coli: SOS repair hypothesis, in: “Molecular and Environmental Aspects of Mutagenesis,” L. Prakash, F. Sherman, M. W. Miller, C. Lawrence, and H. W. Tabor, eds., Charles C. Thomas, Springfield, Illinois, pp. 128–142.Google Scholar
  58. Resnick, M. A., and Setlow, J. K., 1972, Repair of pyrimidine dimer damage induced in yeast by ultraviolet light, J. Bacteriol., 109:979–986.PubMedGoogle Scholar
  59. Sancar, A., and Rupp, W. D., 1983, A novel repair enzyme: UVRABC excision nuclease of E. coli cuts a DNA strand on both sides of the damaged region, Cell, 33:249–260.PubMedCrossRefGoogle Scholar
  60. Setlow, R. B., 1966, Cyclobutane-type pyrimidine dimers in polynucleotides, Science, 153:379–386.PubMedCrossRefGoogle Scholar
  61. Siede, W., and Eckardt, F., 1984, Inducibility of error-prone DNA repair in yeast, Mutat. Res., 129:3–11.PubMedCrossRefGoogle Scholar
  62. von Borstel, R. C., 1966, Effects of radiation on cells, in: “The Biological Basis of Radiation Therapy,” E. E. Schwartz, ed., Lippincott Co., Cleveland, Ohio, pp. 60–125.Google Scholar
  63. von Borstel, R. C., 1982, Thresholds and negative slopes in dose-mutation curves, in: “Environmental Mutagens and Carcinogens,” T. Sugimura, S. Kondo, and H. Takebe, eds., University of Tokyo Press, Tokyo, and Alan R. Liss Inc., New York, pp. 737–741.Google Scholar
  64. von Borstel, R. C., Cain, K. T., and Steinberg, C. M., 1971, Inheritance of spontaneous mutability in yeast, Genetics, 69:17–27.Google Scholar
  65. von Borstel, R. C., Hastings, P. J., and Schroeder, C., 1977, Comparison of replication errors and mutagenic repair as a source of spontaneous mutations, in: “Environmental Mutagens,” H. Böhme and J. Schöneich, eds., Akademie-Verlag, Berlin, pp. 89–93.Google Scholar
  66. Walker, G. C., 1985, Mutagenesis-enhancement by plasmids in mutagenesis tester strains, in: “Basic and Applied Mutagenesis: with Special Reference to Agricultural Chemicals in Developing Countries,” Amir Muhammed and R. C. von Borstel, eds., Plenum Press, New York, pp. 111–120.Google Scholar
  67. Wang, S. Y., 1976, Pyrimidine bimolecular photoproducts, in: “Photochemistry and Photobiology of Nucleic Acids,” Vol. 1, S. Y. Wang, ed., Academic Press, New York, pp. 295–356.Google Scholar
  68. Wang, S. Y., and Varghese, A. J., 1967, Cytosine-thymine addition product from DNA irradiated with ultraviolet light, Biochem. Biophys. Res. Commun., 29:543–549.PubMedCrossRefGoogle Scholar
  69. Witkin, E. M., 1976, Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli, Bacteriol. Rev., 40:869–907.PubMedGoogle Scholar
  70. Witkin, E. M., and George, D. L., 1973, Ultraviolet mutagenesis of polA and uvrA polA derivatives of Escherichia coli B/R: Evidence for an inducible error-prone repair system, Genetics (Suppl.), 73:91–108.PubMedGoogle Scholar
  71. Wood, R. D., Skopek, T. R., and Hutchinson, F., 1984, Changes in DNA base sequence induced by targeted mutagenesis of lambda phage by ultraviolet light, J. Mol. Biol., 173:273–291.PubMedCrossRefGoogle Scholar
  72. Wood, R. W., and Hutchinson, F., 1984, Non-targeted mutagenesis of unirradiated lambda phage in Escherichia coli host cells irradiated with ultraviolet light, J. Mol. Biol., 173:293–305.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • R. C. von Borstel
    • 1
  • P. J. Hastings
    • 1
  1. 1.Department of GeneticsThe University of AlbertaEdmontonCanada

Personalised recommendations