Yeast Genetics pp 109-137 | Cite as

Radiation-Sensitive Mutants and Repair in Yeast

  • J. C. Game
Part of the Springer Series in Molecular Biology book series (SSMOL)

Abstract

Saccharomyces cerevisiae is an excellent organism for studying the genetics of DNA repair processes, since it has a versatile and well-characterized genetic system, and its unicellular nature is convenient for studies in radiation biology. Biochemical studies of DNA repair and related processes have proved more difficult, owing partly to difficulties with DNA-specific labeling. However, substantial progress is now being made in these areas also. Aspects of DNA repair and mutagenesis in yeast have recently been reviewed by several workers, e.g., Haynes and Kunz (1981), Lawrence (1982), and Lemontt (1980). In this chapter I shall briefly outline early studies in the radiation biology of S. cerevisiae. I shall then describe the major classes of radiation-sensitive mutants that have been isolated and discuss their contribution to understanding the genetics of repair in yeast. Finally, I shall describe some recent work indicating that genes that control repair of ionizing-radiation damage are also required for normal meiosis, as well as meiotic and mitotic recombination in yeast, and discuss the role of x-ray-sensitive mutants in current research in these areas.

Keywords

Recombination Resis Pyrimidine Deoxythymidine Nucleoside 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adler, H. I. (1966). The genetic control of radiation sensitivity in microorganisms. Adv. Radiation Biol. 2:167–192.Google Scholar
  2. Averbeck, D. (1970). Isolierung and Characterisierung von drei UV-sensiblen Saccharomyces-Mutmten. Dissertation, Freie Universitat Berlin.Google Scholar
  3. Averbeck, D., Laskowski, W., Eckardt, F., Lehmann-Brauns, E. (1970). Four radiation-sensitive mutants of Saccharomyces. Mol. Gen. Genet. 107:117–127.PubMedCrossRefGoogle Scholar
  4. Baker, B., Carpenter, A. T. C., Esposito, M. S., Esposito, R. E., Sandler, L. (1976). The genetic control of meiosis. Ann. Rev. Genet. 10:53–134.PubMedCrossRefGoogle Scholar
  5. Beams, C. A., Mortimer, R. K., Wolfe, R. G., Tobias, C. A. (1954). The relation of radioresistance in budding in Saccharomyces cerevisiae. Arch. Biochem. Biophys. 49:110–122.CrossRefGoogle Scholar
  6. Brendel, M., Haynes, R. H. (1973). Interactions among genes controlling sensitivity to radiation and alkylation in yeast. Mol. Gen. Genet. 125:197–216.PubMedCrossRefGoogle Scholar
  7. Brunborg, G., Williamson, D. H. (1978). The relevance of the nuclear division cycle to radiosensitivity in yeast. Mol. Gen. Genet. 162:277–286.Google Scholar
  8. Brunborg, G., Resnick, M. A., Williamson, D. H. (1980). Cell-cycle-specific repair of DNA double-strand breaks in Saccharomyces cerevisiae. Radiation Res. 82:547–548.PubMedCrossRefGoogle Scholar
  9. Budd, M., Mortimer, R. K. (1982). Repair of double-strand breaks in a temperatureGoogle Scholar
  10. conditional radiation-sensitive mutant of Saccharomyces cerevisiae. Mutation Res. 103:19–26.Google Scholar
  11. Chanet, R., Williamson, D. H., Moustacchi, E. (1973). Cyclic variations in killing and “petite” mutagenesis induced by ultraviolet light in synchronized yeast strains. Biochem. Biophys. Acta (Amst.) 324:290–299.Google Scholar
  12. Coulondre, C., Miller, J. H., Farnbaught, P. J., Gilbert, W. (1978). Molecular basis of base substitution hotspots in Escherichia coli. Nature (London) 274:775–780.CrossRefGoogle Scholar
  13. Cox, B. S., Game, J. C. (1974). Repair systems in Saccharomyces. Mutation Res. 26:257–264.PubMedCrossRefGoogle Scholar
  14. Cox, B. S., Parry, J. M. (1968). The isolation, genetics, and survival characteristics of ultraviolet light-sensitive mutants in yeast. Mutation Res. 6:37–55.PubMedCrossRefGoogle Scholar
  15. Dowling, E. D. (1981). Meiotic recombination and sporulation in repair-deficient strains of yeast. Ph.D. Thesis, University of California, Berkeley, California.Google Scholar
  16. di Caprio L., Cox, B. S. (1981). DNA synthesis in UV-irradiated yeast. Mutat. Res. 82:69–85.PubMedCrossRefGoogle Scholar
  17. Eckardt, F., Kowalski, S., Laskowski, W. (1975). The effect of three rad genes on UV-induced mutation rates in haploid and diploid Saccharomyces cells. Molec. Gen. Genetics 136:261–272.CrossRefGoogle Scholar
  18. Elkind, M. M, Sutton, H. (1959). The relationship between division and X-ray sensitivity, ultraviolet sensitivity, and photoreactivation in yeast. Radiat. Res. 10:283–295.PubMedCrossRefGoogle Scholar
  19. Fabre, F. (1971) A UV-supersensitive mutant in the yeast Schizosaccharomyces pombe: Evidence for two repair pathways. Mol. Gen. Genet. 110:134–143.PubMedGoogle Scholar
  20. Fath, W. W., Brendel, M., Laskowski, W., Lehmann-Brauns, E. (1974). Economizing DNA-specific labelling by deoxythymidine-5-monophosphate in Saccharomyces cerevisiae. Mol. Gen. Genet. 132:335–345.PubMedCrossRefGoogle Scholar
  21. Friis, J., Roman, H. (1968). The effect of the mating type alleles on intragenic recombination in yeast. Genetics 59:33–36.PubMedGoogle Scholar
  22. Game, J. C. (1971). A study of radiation-sensitive mutants in yeast. D. Phil. Thesis, University of Oxford.Google Scholar
  23. Game, J. C., Cox, B. S. (1971). Allelism tests of mutants affecting sensitivity to radiation in yeast and a proposed nomenclature. Mutation Res. 12:328–331.CrossRefGoogle Scholar
  24. Game, J. C., Cox, B. S. (1972). Epistatic interactions between four rad loci in yeast. Mutation Res. 16:353–362.PubMedCrossRefGoogle Scholar
  25. Game, J. C., Cox, B. S. (1973). Synergistic interactions between rad mutations in yeast. Mutation Res. 20:35–44.PubMedCrossRefGoogle Scholar
  26. Game, J. C., Mortimer, R. K. (1974). A genetic study of X-ray sensitive mutants in yeast. Mutation Res. 24:281–292.PubMedCrossRefGoogle Scholar
  27. Game, J. C., Zamb, T. J., Braun, R. J., Resnick, M., Roth, R. M. (1980). The role of radiation (rad) genes in meiotic recombination in yeast. Genetics 94:51–68.PubMedGoogle Scholar
  28. Game, J. C., Schild, D., Esposito, R. Easton (1981). The meiotic phenotype of the rad 57-1 mutation. Abst. in: The Molecular Biology of Yeast, meeting abstracts, Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory.Google Scholar
  29. Harm, H. (1976). Repair of UV-irradiated biological systems: Photoreactivation. In: Photochemistry and Photobiology of Nucleic Acids, Vol. II, edited by S. Y. Wang. New York: Academic Press, pp. 219–263.Google Scholar
  30. Harm, W. (1963). Mutants of phage T4 with increased sensitivity to ultraviolet. Virology 19:66–71.PubMedCrossRefGoogle Scholar
  31. Hartwell, L. H. (1971). Genetic control of the cell division cycle in yeast II. Genes controlling DNA replication and its initiation. J. Mol. Biol. 59:183–194.PubMedCrossRefGoogle Scholar
  32. Haseltine, W. A., Gordon, L. K., Lindan, C. P., Grafstrom, R., Shaper, N. L., Grossman, L. (1980). Cleavage of pyrimidine dimers in specific DNA sequences by a pyrimidine dimer DNA-glycoslyase of M. luteus, Nature (London) 285:634–641.CrossRefGoogle Scholar
  33. Hastings, P. J., Quah, S. K., Von Borstel, R. C. (1976). Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA. Nature 264:719–722.PubMedCrossRefGoogle Scholar
  34. Haynes, R. H., Kunz, B. A. (1981). DNA repair and mutagenesis in yeast. In: The Molecular Biology of the Yeast Saccharomyces, edited by J. Strathern, E. Jones, J. Broach. Cold Spring Harbor, N.Y.: Cold Spring Harbor Lab., p. 371.Google Scholar
  35. Ho, K. S. Y., Mortimer, R. K. (1973). Induction of dominant lethality by X-rays in a radiosensitive strain of yeast. Mutation Res. 20:45–51.PubMedCrossRefGoogle Scholar
  36. Ho, K. S. Y. (1975). Induction of DNA double-strand breaks by X-rays in a radiosensitive strain of the yeast Saccharomyces cerevisiae. Mutation Res. 30:327–334.PubMedCrossRefGoogle Scholar
  37. Ho, K., Mortimer, R. K. (1975). Two mutations which confer temperature-sensitive radiation sensitivity in the yeast Saccharomyces cervisiae. Mutation Res. 33:157–164.PubMedCrossRefGoogle Scholar
  38. Holliday, R. (1965). Radiation sensitive mutants of Ustilago maydis. Mutation Res. 2:557–559.PubMedCrossRefGoogle Scholar
  39. Hunnable, E., Cox, B. S. (1971). The genetic control of dark repair in yeast. Mutation Res. 13:297–309.CrossRefGoogle Scholar
  40. Jannsen, S., Witte, I., Megnet, R. (1973). Mutants for the specific labelling of DNA in Saccharomyces cerevisiae. Biochem. Biophys. Acta 299:681–685.Google Scholar
  41. Johnston, L. H., Nasmyth, K. A. (1978). Saccharomyces cerevisiae cell cycle mutant cdc9 is defective in DNA ligase. Nature 274:891–893.PubMedCrossRefGoogle Scholar
  42. Kern, R., Zimmerman, F. K. (1978). The influence of defects in excision and error prone repair on spontaneous and induced mitotic recombination and mutation in Saccharomyces cervisiae. Molec. Gen. Genet. 161:81–88.PubMedCrossRefGoogle Scholar
  43. Klapholz, S., Esposito, R. (1980a). Isolation of spo12–1 and spo13–1 from a natural variant of yeast that undergoes a single meiotic division. Genetics 96:567–588.PubMedGoogle Scholar
  44. Klapholz, S., Esposito, R. (1980b). Recombination and chromosome segregation during the single division meiosis in spo12–1 and spo13–1 diploids. Genetics 96:589–611.PubMedGoogle Scholar
  45. Koval’tsova, S. V., Zheleznyakova, N. Y., Zakharov, I. A. (1970). Repair and mutagenesis communication I. Influence of mutations of radiosensitivity on UV-induced mutagenesis in Saccharomyces cerevisiae. Genetika 6:78–85.Google Scholar
  46. Lacassagne, A., Holweck, F. 1930 Sur la radiosensibilité de la levure Saccharomyces ellipsoideus. Compt. rend de la Soc. de Biol., Paris, 104:1221–1223.Google Scholar
  47. Laskowski, W. 1960 Inaktivierungsversuche mit homozygoten hefestammen verschiedenen ploidiegrades. Z. Naturforsch 15b:495–506.Google Scholar
  48. Latarjet, Raymond, Ephrussi, Boris (1949). Courbes de survie de levures haploides et diploids soumises aux rayons X. Comptes Rendus, Académie des Sciences, Paris, 229:306–308.Google Scholar
  49. Lawrence, C. W. (1982). Mutagenesis in Saccharomyces cerevisiae, Adv. Genet. 21:173–254.Google Scholar
  50. Lawrence, C. W., Christensen, R. (1976). UV-mutagenesis in radiation-sensitive strains of yeast. Genetics 82:207–232.PubMedGoogle Scholar
  51. Lemontt, J. F. (1971). Mutants of yeast defective in mutation induced by ultraviolet light. Genetics 68:21–33.PubMedGoogle Scholar
  52. Lemontt, J. F. (1980). Genetic and physiological factors affecting repair and mutagenesis in yeast. In: DNA Repair and Mutagenesis in Eukaryotes, edited by F. J. de Serres et al. New York: Plenum Press, p. 85.Google Scholar
  53. Lippke, J. A., Gordon, L. K., Brash, D. E., Haseltine, W. A. (1981). Distribution of UV light-induced damage in a defined sequence of human DNA: Detection of alkali-sensitive lesions at pyrimidine nucleoside-cytidine sequences. Proc. Natl. Acad. Sci. USA 78:3388–3392.PubMedCrossRefGoogle Scholar
  54. Little, J. G., Haynes, R. H. (1979). Isolation and characterization of yeast mutants auxotrophic for 2-deoxythymidine 5-monophosphate. Molec. Gen. Genet. 168:141–151.Google Scholar
  55. Malone, R., Esposito, R. (1980). The RAD52 gene is required for homothallic inter-conversion of mating types and spontaneous mitotic recombination. Proc. Natl. Acad. Sci. USA 77:503–507.PubMedCrossRefGoogle Scholar
  56. Malone, R. E., Esposito, R. (1981). Recombinationless meiosis in yeast. Mol. Cell. Biol. 1:891–901.Google Scholar
  57. McKee, R. H., Lawrence, C. W. (1979). Genetic analysis of 7-ray mutagenesis in yeast I. Reversion in radiation-sensitive strains. Genetics 93:361–373.PubMedGoogle Scholar
  58. McKee, R. H., Lawrence, C. W. (1980). Genetic analysis of γ-ray mutagenesis in yeast III. Double mutant strains. Mutation Res. 70:37–48.PubMedCrossRefGoogle Scholar
  59. Morrison, D. P., Hastings, P. J. (1979). Characterization of the mutator mutation mut5-l. Molec. Gen. Genet. 175:57–65.PubMedCrossRefGoogle Scholar
  60. Mortimer, R. K. (1958). Radiobiological and genetic studies on a polyploid series (Haploid to Hexaploid) of Saccharomyces cerevisiae. Radiation Res. 9:312–326.PubMedCrossRefGoogle Scholar
  61. Mortimer, R. K., Contopoulou, R., Schild, D. (1981). Mitotic chromosome loss in a radiation-sensitive strain of the yeast Saccharomyces cerevisiae, Proc. Natl. Acad. Sci. USA 78:5778–5782.PubMedCrossRefGoogle Scholar
  62. Nakai, S., Matsumoto, S. (1967). Two types of radiation-sensitive mutants in yeast. Mutation Res. 4:129–136.PubMedCrossRefGoogle Scholar
  63. Parry, J. M., Cox, B. S. (1968). The effects of dark holding and photoreactivation on ultraviolet light-induced mitotic recombination and survival in yeast. Genet. Res. Camb. 12:187–198.CrossRefGoogle Scholar
  64. Perper, T. (1975). Cyclic X-ray resistance to lethal and non-lethal damage in Saccharomyces cerevisiae. Radiation Res. 63:97–118.PubMedCrossRefGoogle Scholar
  65. Prakash, L. (1975). Repair of pyrimidine dimers in nuclear and mitochondrial DNA of yeast irradiated with low doses of ultraviolet light. J. Mol. Biol. 98:781–795.PubMedCrossRefGoogle Scholar
  66. Prakash, L. (1977a). Repair of pyrimidine dimers in radiation-sensitive mutants rad3 rad4 rad6 and rad9 of Saccharomyces cerevisiae. Mutat. Res. 45:13–20.PubMedCrossRefGoogle Scholar
  67. Prakash, L. (1977b). Defective thymine dimer excision in radiation-sensitive mutants rad10 and rad16 of Saccharomyces cerevisiae. Mol. Gen. Genet. 152:125–128.PubMedCrossRefGoogle Scholar
  68. Prakash, L. (1981). Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations. Mol. Gen. Genet. 184:471–478.PubMedCrossRefGoogle Scholar
  69. Prakash, L., Prakash, S. (1977). Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae. Genetics 86:33–55.PubMedGoogle Scholar
  70. Prakash, L., Prakash, S. (1979). Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14 and MMS19. Molec. Gen. Genet. 176:351–359.PubMedCrossRefGoogle Scholar
  71. Prakash, L., Hinkle, D., Prakash, S. (1979). Decreased UV mutagenesis in cdc8, a DNA replication mutant of Saccharomyces cerevisiae. Molec. Gen. Genet. 172:249–258.PubMedCrossRefGoogle Scholar
  72. Prakash, S., Prakash, L., Burke, W., Montelone, B. A. (1980). Effects of the RAD52 gene on recombination in Saccharomyces cerevisiae. Genetics 94:31–50.PubMedGoogle Scholar
  73. Resnick, M. A. (1969). A photoreactivationless mutant of Saccharomyces cerevisiae. Photochem. Photobiol. 9:307–312.CrossRefGoogle Scholar
  74. Resnick, M. A., Martin, P. (1976). The repair of double-stranded breaks in the nuclear DNA of Saccharomyces cerevisiae and its genetic control. Molec. Gen. Genet. 143:119–129.PubMedCrossRefGoogle Scholar
  75. Resnick, M. A., Setlow, J. K. (1972). Repair of pyrimidine dimer damage induced in yeast by ultraviolet light. J. Bacteriol. 109:979–986.PubMedGoogle Scholar
  76. Resnick, M. A., Kasimos, J. N., Game, J. C., Braun, R. J., Roth, R. M. (1981). Changes in DNA during meiosis in a repair-deficient mutant (rad52) of yeast. Science 212:543–545.PubMedCrossRefGoogle Scholar
  77. Reynolds, R. J. (1978). Removal of pyrimidine dimers from Saccharomyces cerevisiae nuclear DNA udner non-growth conditions as detected by a sensitive enzymatic assay. Mutat. Res. 50:43–56.PubMedCrossRefGoogle Scholar
  78. Reynolds, R. J., Friedberg, E. C. (1981). Molecular mechanisms of pyrimidine dimer excision in Saccharomyces cerevisiae: Incision of ultraviolet-irradiated deoxyribo-nucleic acid in vivo. J. Bacteriol. 146:692–704.PubMedGoogle Scholar
  79. Reynolds, R. J., Love, J. D., Friedberg, E. C. (1981). Molecular mechanisms of pyrimidine dimer excision on Saccharomyces cerevisiae: Excision of dimers in cell extracts. J. Bacteriol. 147:705–708.PubMedGoogle Scholar
  80. Rupp, W. D., Howard-Flanders, P. (1968). Discontinuities in the DNA synthesized in an excision-defective strain of Escherichia coli following ultraviolet irradiation. J. Mol. Biol. 31, 291–304.PubMedCrossRefGoogle Scholar
  81. Saeki, T., Machida, I., Nakai, S. (1981). Genetic control of diploid recovery after γ-irradiation in the yeast Saccharomyces cerevisiae. Mutation Res. 73:251–265.Google Scholar
  82. Saracheck, A. (1954). A comparative study of the retardation of budding and cellular inactivation by ultraviolet radiation in polyploid Saccharomyces with special reference to photoreactivation. Cytologia 19:77–85.Google Scholar
  83. Setlow, J. K., Boling, M. E., Bollum, F. J. (1965). The chemical nature of photoreactivable lesions in DNA. Proc. Natl. Acad. Sci. USA 53:1430–1436.PubMedCrossRefGoogle Scholar
  84. Sherman, F., Roman, H. (1963). Evidence for two types of allelic recombination in yeast. Genetics 48:255–261.PubMedGoogle Scholar
  85. Snow, R. (1967). Mutants of yeast sensitive to ultraviolet light. J. Bacteriol. 94:571–575.PubMedGoogle Scholar
  86. Snow, R. (1968). Recombination in ultraviolet-sensitive strains of Saccharomyces cerevisiae. Mutation Res. 6:409–418.PubMedCrossRefGoogle Scholar
  87. Unrau, P., Wheatcroft, R., Cox, B. S. (1971). The excision of pyrimidine dimers from DNA of ultraviolet irradiated yeast. Molec. Gen. Genet. 354:359–362.Google Scholar
  88. Unrau, P., Wheatcroft, R., Cox, B., Olive, T. (1973). The formation of pyrimidine dimers in the DNA of fungi and bacteria. Biochem. Biophys. Acta. 312:626–632.Google Scholar
  89. Wickner, R. B. (1974). Mutants of Saccharomyces cerevisiae that incorporate deoxythimidine-5-monophosphate into deoxyribonucleic acid in vivo. J. Bacteriol. 117:252–260.PubMedGoogle Scholar
  90. Wilcox, D. R., Prakash, Louise (1981). Incision and post incision steps of pyrimidine dimer removal in excision-defective mutants of Saccharomyces cerevisiae. J. Bacteriol. 148:618–623.PubMedGoogle Scholar
  91. Zakharov, I. A., Kozhina, T. N. (1967). A yeast mutant hypersensitive to ultraviolet rays. Dokl. Acad. Nauk. SSSR, 176:1417.Google Scholar
  92. Zirkle, Raymond E., Tobias, Cornelius A. (1953). Effects of ploidy and linear energy transfer on radiobiological survival curves. Arch. Biochem. and Biophys. 47:282–306.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1983

Authors and Affiliations

  • J. C. Game
    • 1
  1. 1.360 Donner LaboratoryLawrence Berkeley LaboratoryBerkeleyUSA

Personalised recommendations