Mechanisms of UV Mutagenesis in Yeast
UV mutagenesis in yeast depends on the function of the RAD6 locus, a gene that is also responsible for a substantial fraction of wild-type resistance, suggesting that this eukaryote may possess a misrepair mechanism analogous to that proposed for Escherichia coli. The molecular mechanism responsible for RAD6 repair or recovery is not yet known, but it is different from either excision or recombination-dependent repair, processes carried out by the other two main repair pathways in yeast. RAD6-dependent mutagenesis has been found to have the following characteristics.
It is associated at best with only a small fraction of RAD6- dependent repair, the majority of the sensitivity of rad6 mutants being due to their lack of nonmutagenic repair. SRS2 metabolic suppressors restore a substantial fraction of UV resistance to rad6 mutants but do not restore their UV mutability. Strains containing mutations at loci (rev, umr) that are probably more directly involved in mutagenesis are only mildly sensitive, and there is a poor correlation between their sensitivity and mutational deficiency.
UV mutagenesis appears to require a large number of gene functions, perhaps ten or more. Where examined in detail, these genes have been found to be concerned in the production of only a specific range of mutational events, not all of them.
Mating experiments have shown that a substantial fraction, probably 40% or more, of UV-induced mutations are untargeted, that is, occur in lesion-free regions of DNA, UV irradiation, therefore, produces a general reduction in the normally high f fidelity with which DNA is replicated on undamaged templates. It does not appear to be necessary for the causal lesion to be present in the same chromosome as the mutation it induces. The reduction in fidelity may be the consequence of the production of a diffusible factor in UV-irradiated cells, but definite evidence supporting this proposal has not yet been obtained.
KeywordsMating Experiment Opposite Mating Type Causal Lesion Frameshift Event Ochre Mutant
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