Skip to main content
Genetics logoLink to Genetics
. 1994 Jul;137(3):637–646. doi: 10.1093/genetics/137.3.637

Specificity of the Yeast Rev3Δ Antimutator and Rev3 Dependency of the Mutator Resulting from a Defect (Rad1Δ) in Nucleotide Excision Repair

H Roche 1, R D Gietz 1, B A Kunz 1
PMCID: PMC1206023  PMID: 8088509

Abstract

The yeast REV3 gene has been predicted to encode a DNA polymerase specializing in translesion synthesis. This polymerase likely participates in spontaneous mutagenesis, as rev3 mutants have an antimutator phenotype. Translesion synthesis also may be necessary for the mutator caused by a RAD1 (nucleotide excision repair) deletion (rad1Δ). To further examine the role of REV3 in spontaneous mutagenesis, we characterized SUP4-o mutations that arose spontaneously in strains having combinations of normal or mutant REV3 and RAD1 alleles. The largest fraction of the rev3Δ-dependent mutation rate decrease was observed for single base-pair substitutions and deletions, although the rates of all mutational classes detected in the RAD1 background were reduced by at least 30%. Interestingly, inactivation of REV3 was associated with a doubling of the number of sites at which the retrotransposon Ty inserted. rev3Δ also greatly diminished the magnitude of the rad1Δ mutator, but not to the rev3Δ antimutator level, implicating REV3-dependent and independent processes in the rad1Δ mutator effect. However, the specificity of the rev3Δ antimutator suggested that the same REV3-dependent processes gave rise to the majority of spontaneous mutations in the RAD1 and rad1Δ strains.

Full Text

The Full Text of this article is available as a PDF (985.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams W. T., Skopek T. R. Statistical test for the comparison of samples from mutational spectra. J Mol Biol. 1987 Apr 5;194(3):391–396. doi: 10.1016/0022-2836(87)90669-3. [DOI] [PubMed] [Google Scholar]
  2. Alani E., Cao L., Kleckner N. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics. 1987 Aug;116(4):541–545. doi: 10.1534/genetics.112.541.test. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Amariglio N., Rechavi G. Insertional mutagenesis by transposable elements in the mammalian genome. Environ Mol Mutagen. 1993;21(3):212–218. doi: 10.1002/em.2850210303. [DOI] [PubMed] [Google Scholar]
  4. Ames B. N., Shigenaga M. K., Hagen T. M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915–7922. doi: 10.1073/pnas.90.17.7915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Basak J., Mukherjee U., Chatterjee S. N. Adaptive response of Vibrio cholerae and Escherichia coli to nitrofurantoin. Environ Mol Mutagen. 1992;20(1):53–60. doi: 10.1002/em.2850200109. [DOI] [PubMed] [Google Scholar]
  6. Cassier-Chauvat C., Moustacchi E. Allelism between pso1-1 and rev3-1 mutants and between pso2-1 and snm1 mutants in Saccharomyces cerevisiae. Curr Genet. 1988;13(1):37–40. doi: 10.1007/BF00365754. [DOI] [PubMed] [Google Scholar]
  7. Cassier C., Chanet R., Henriques J. A., Moustacchi E. The effects of three PSO genes on induced mutagenesis : a novel class of mutationally defective yeast. Genetics. 1980 Dec;96(4):841–857. doi: 10.1093/genetics/96.4.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooper D. N., Krawczak M. The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions. Hum Genet. 1990 Jun;85(1):55–74. doi: 10.1007/BF00276326. [DOI] [PubMed] [Google Scholar]
  9. Drake J. W. General antimutators are improbable. J Mol Biol. 1993 Jan 5;229(1):8–13. doi: 10.1006/jmbi.1993.1002. [DOI] [PubMed] [Google Scholar]
  10. Drake J. W. Spontaneous mutation. Annu Rev Genet. 1991;25:125–146. doi: 10.1146/annurev.ge.25.120191.001013. [DOI] [PubMed] [Google Scholar]
  11. Fijalkowska I. J., Dunn R. L., Schaaper R. M. Mutants of Escherichia coli with increased fidelity of DNA replication. Genetics. 1993 Aug;134(4):1023–1030. doi: 10.1093/genetics/134.4.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Friedberg E. C. Deoxyribonucleic acid repair in the yeast Saccharomyces cerevisiae. Microbiol Rev. 1988 Mar;52(1):70–102. doi: 10.1128/mr.52.1.70-102.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gietz D., St Jean A., Woods R. A., Schiestl R. H. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 1992 Mar 25;20(6):1425–1425. doi: 10.1093/nar/20.6.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Giroux C. N., Mis J. R., Pierce M. K., Kohalmi S. E., Kunz B. A. DNA sequence analysis of spontaneous mutations in the SUP4-o gene of Saccharomyces cerevisiae. Mol Cell Biol. 1988 Feb;8(2):978–981. doi: 10.1128/mcb.8.2.978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heddle J. A., Shepson P. B., Gingerich J. D., So K. W. Mutagenicity of peroxyacetyl nitrate (PAN) in vivo: tests for somatic mutations and chromosomal aberrations. Environ Mol Mutagen. 1993;21(1):58–66. doi: 10.1002/em.2850210108. [DOI] [PubMed] [Google Scholar]
  16. Henriques J. A., Brendel M. The role of PSO and SNM genes in DNA repair of the yeast Saccharomyces cerevisiae. Curr Genet. 1990 Dec;18(5):387–393. doi: 10.1007/BF00309906. [DOI] [PubMed] [Google Scholar]
  17. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kang X. L., Yadao F., Gietz R. D., Kunz B. A. Elimination of the yeast RAD6 ubiquitin conjugase enhances base-pair transitions and G.C----T.A transversions as well as transposition of the Ty element: implications for the control of spontaneous mutation. Genetics. 1992 Feb;130(2):285–294. doi: 10.1093/genetics/130.2.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Knapp G., Beckmann J. S., Johnson P. F., Fuhrman S. A., Abelson J. Transcription and processing of intervening sequences in yeast tRNA genes. Cell. 1978 Jun;14(2):221–236. doi: 10.1016/0092-8674(78)90109-5. [DOI] [PubMed] [Google Scholar]
  20. Kohalmi L., Kunz B. A. In vitro mutagenesis of the yeast SUP4-o gene to identify all substitutions that can be detected in vivo with the SUP4-o system. Environ Mol Mutagen. 1992;19(4):282–287. doi: 10.1002/em.2850190404. [DOI] [PubMed] [Google Scholar]
  21. Kohalmi S. E., Glattke M., McIntosh E. M., Kunz B. A. Mutational specificity of DNA precursor pool imbalances in yeast arising from deoxycytidylate deaminase deficiency or treatment with thymidylate. J Mol Biol. 1991 Aug 20;220(4):933–946. doi: 10.1016/0022-2836(91)90364-c. [DOI] [PubMed] [Google Scholar]
  22. Kramer W., Kramer B., Williamson M. S., Fogel S. Cloning and nucleotide sequence of DNA mismatch repair gene PMS1 from Saccharomyces cerevisiae: homology of PMS1 to procaryotic MutL and HexB. J Bacteriol. 1989 Oct;171(10):5339–5346. doi: 10.1128/jb.171.10.5339-5346.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kunkel T. A. Biological asymmetries and the fidelity of eukaryotic DNA replication. Bioessays. 1992 May;14(5):303–308. doi: 10.1002/bies.950140503. [DOI] [PubMed] [Google Scholar]
  24. Kunz B. A., Kang X. L., Kohalmi L. The yeast rad18 mutator specifically increases G.C----T.A transversions without reducing correction of G-A or C-T mismatches to G.C pairs. Mol Cell Biol. 1991 Jan;11(1):218–225. doi: 10.1128/mcb.11.1.218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kunz B. A., Pierce M. K., Mis J. R., Giroux C. N. DNA sequence analysis of the mutational specificity of u.v. light in the SUP4-o gene of yeast. Mutagenesis. 1987 Nov;2(6):445–453. doi: 10.1093/mutage/2.6.445. [DOI] [PubMed] [Google Scholar]
  26. Lawrence C. W., Christensen R. B. Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. III. rev3 mutant strains. Genetics. 1979 Jun;92(2):397–408. doi: 10.1093/genetics/92.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lawrence C. W., Christensen R. UV mutagenesis in radiation-sensitive strains of yeast. Genetics. 1976 Feb;82(2):207–232. doi: 10.1093/genetics/82.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lawrence C. W. Mutagenesis in Saccharomyces cerevisiae. Adv Genet. 1982;21:173–254. doi: 10.1016/s0065-2660(08)60299-0. [DOI] [PubMed] [Google Scholar]
  29. Lawrence C. W., O'Brien T., Bond J. UV-induced reversion of his4 frameshift mutations in rad6, rev1, and rev3 mutants of yeast. Mol Gen Genet. 1984;195(3):487–490. doi: 10.1007/BF00341451. [DOI] [PubMed] [Google Scholar]
  30. Liebman S. W., Newnam G. A ubiquitin-conjugating enzyme, RAD6, affects the distribution of Ty1 retrotransposon integration positions. Genetics. 1993 Mar;133(3):499–508. doi: 10.1093/genetics/133.3.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993 Apr 22;362(6422):709–715. doi: 10.1038/362709a0. [DOI] [PubMed] [Google Scholar]
  32. Loeb L. A., Cheng K. C. Errors in DNA synthesis: a source of spontaneous mutations. Mutat Res. 1990 May;238(3):297–304. doi: 10.1016/0165-1110(90)90021-3. [DOI] [PubMed] [Google Scholar]
  33. Loeb L. A. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991 Jun 15;51(12):3075–3079. [PubMed] [Google Scholar]
  34. McIntosh E. M. MCB elements and the regulation of DNA replication genes in yeast. Curr Genet. 1993 Sep;24(3):185–192. doi: 10.1007/BF00351790. [DOI] [PubMed] [Google Scholar]
  35. Mis J. R., Kunz B. A. Analysis of mutations induced in the SUP4-o gene of Saccharomyces cerevisiae by cis-diammine dichloroplatinum(II). Carcinogenesis. 1990 Apr;11(4):633–638. doi: 10.1093/carcin/11.4.633. [DOI] [PubMed] [Google Scholar]
  36. Newlon C. S. Yeast chromosome replication and segregation. Microbiol Rev. 1988 Dec;52(4):568–601. doi: 10.1128/mr.52.4.568-601.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. O'Day C. L., Burgers P. M., Taylor J. S. PCNA-induced DNA synthesis past cis-syn and trans-syn-I thymine dimers by calf thymus DNA polymerase delta in vitro. Nucleic Acids Res. 1992 Oct 25;20(20):5403–5406. doi: 10.1093/nar/20.20.5403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ramel C. The nature of spontaneous mutations. Mutat Res. 1989 May;212(1):33–42. doi: 10.1016/0027-5107(89)90020-1. [DOI] [PubMed] [Google Scholar]
  39. Sargentini N. J., Smith K. C. Spontaneous mutagenesis: the roles of DNA repair, replication, and recombination. Mutat Res. 1985 Jul;154(1):1–27. doi: 10.1016/0165-1110(85)90007-7. [DOI] [PubMed] [Google Scholar]
  40. Schiestl R. H., Gietz R. D. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr Genet. 1989 Dec;16(5-6):339–346. doi: 10.1007/BF00340712. [DOI] [PubMed] [Google Scholar]
  41. Singhal R. K., Hinkle D. C., Lawrence C. W. The REV3 gene of Saccharomyces cerevisiae is transcriptionally regulated more like a repair gene than one encoding a DNA polymerase. Mol Gen Genet. 1992 Dec;236(1):17–24. doi: 10.1007/BF00279638. [DOI] [PubMed] [Google Scholar]
  42. Smith K. C., Sargentini N. J. Metabolically-produced 'UV-like' DNA damage and its role in spontaneous mutagenesis. Photochem Photobiol. 1985 Dec;42(6):801–803. doi: 10.1111/j.1751-1097.1985.tb01652.x. [DOI] [PubMed] [Google Scholar]
  43. Wintersberger U. On the origins of genetic variants. FEBS Lett. 1991 Jul 22;285(2):160–164. doi: 10.1016/0014-5793(91)80796-6. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES