Genetic Analysis of Error-Prone Repair Systems in Saccharomyces cerevisiae
The manner in which ultraviolet induced mutagenesis occurs in yeast is discussed and compared with ultraviolet mutagenesis in Escherichia coli. In both excision proficient and excision deficient strains of Escherichia coli, mutations arise as the square of the ultraviolet dose whereas in yeast, mutations arise as the square of the dose only in excision proficient strains. In excision defective yeast strains, mutations induced by ultraviolet arise with linear kinetics. Ultraviolet irradiation of excision proficient haploid or diploid yeast during G1 results in fixation of mutation in both DNA strands prior to DNA replication, whereas in excision defective strains, the frequency of two strand mutations is very low, and the frequency of one strand mutations and mutations appearing in the second post irradiation mitotic division is increased. All of these results in yeast can be explained by error prone excision repair of two closely spaced dimers in opposite DNA strands in excision proficient strains and occasional error prone filling of postreplication gaps, which are not usually overlapping daughter strand gaps, in excision defective yeast. The dependence of UV mutagenesis on functional RAD6, REV3, CDC8 and MMS3 gene functions is discussed. The MMS3 function appears to be required for UV mutagenesis in a./α diploids but is dispensible in a /a or α/α diploids and in haploids, suggesting that differences exist between error prone repair processes in haploids, a/a, α/α diploids vs. a/α diploids.
Alkylating agent induced mutations in yeast depend on functional RAD6, RAD9, RAD51 and RAD52 genes. Different alleles of the RAD52 locus differ in their effects on ethyl methanesulfonate induced mutations of different sites within the same gene. Misreplication of O6-alkyl guanine probably does not account for most of the mutations induced by alkylating agents in yeast: instead, they probably result from RAD6-dependent error prone repair of gaps opposite O6-alkyl guanine. Error prone repair pathways for repair of radiation damage differ in some respects from error prone repair of damage induced by chemical agents.
KeywordsError Prone Repair Missense Allele Ochre Mutant Ultraviolet Mutagenesis Strand Mutation
Unable to display preview. Download preview PDF.
- 1.Averbeck, D., W. Laskowski, F. Eckardt, and E. Lehmann-Brauns, Four radiation sensitive mutants of Saccharomyces. Survival after UV-and X ray-irradiation as well as UV-induced reversion rates from isoleucine-valine dependence to independence, Mol. Gen. Genet., 107 (1970) 117–127.PubMedCrossRefGoogle Scholar
- 16.Green, M. H. L., On the possible immunity of newly synthesized DNA to error-prone repair, Mutat. Res., 44 (1977) 161–163.Google Scholar
- 26.Lawley, P. D., Alkylation of nucleic acids and mutagenesis, In: Molecular and Environmental Aspects of Mutagenesis, L. Prakash, F. Sherman, M. W. Miller, C. W. Lawrence, and H. W. Taber, Eds., Charles C Thomas, Springfield, Ill., 1974, pp. 17–33.Google Scholar
- 46.Prakash, L. and S. Prakash, Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14 and MMS19, Mol. Gen. Genet., (1979) in press.Google Scholar
- 47.Prakash, L., and S. Prakash, unpublished results.Google Scholar
- 49.Prakash, S., L. Prakash, W. Burke, and B. Montelone, Effects of the RAD52 gene on recombination in Saccharomyces cerevisiae, Genetics, in press (1979).Google Scholar
- 50.Quah, S.-K., personal communication, University of Alberta.Google Scholar
- 51.Radman, M., 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. W. Lawrence, and H. W. Taber, Charles C Thomas, Springfield, Ill., 1974, pp. 128–142.Google Scholar
- 56.Sedgwick, S. G., Misrepair of overlapping daughter strand gaps as a possible mechanism for UV induced mutagenesis in uvr strains of Escherichia coli: a general model for induced mutagenesis by misrepair (SOS repair) of closely spaced lesions, Mutat. Res., 41 (1976) 185–200.PubMedCrossRefGoogle Scholar
- 58.Smith, K. C., D. A. Youngs, E. van der Schueren, K. M. Carlson, and N. J. Sargentini, Excision repair and mutagenesis are complex processes, In: DNA Repair Mechanisms, P. C. Hanawalt, E. C. Friedberg, and C. F. Fox, eds., Academic Press, New York, Vol. 9, 1978, pp. 247–250.Google Scholar