DNA polymerase zeta generates clustered mutations during bypass of endogenous DNA lesions in Saccharomyces cerevisiae.

Abstract:

Multiple sequence changes that are simultaneously introduced in a ...
Multiple sequence changes that are simultaneously introduced in a single DNA transaction have a higher probability of altering gene function than do single base substitutions. DNA polymerase zeta (Pol ζ) has been shown to introduce such clustered mutations under specific selective and/or DNA damage-producing conditions. In this study, a forward mutation assay was used to determine the specificity of spontaneous mutations generated in Saccharomyces cerevisiae when either wild-type Pol ζ or a mutator Pol ζ variant (rev3-L979F) bypasses endogenous lesions. Mutagenesis in strains proficient for nucleotide excision repair (NER) was compared to mutagenesis in NER-deficient strains that retain unrepaired endogenous DNA lesions in the genome. Compared to NER-proficient strains, NER-deficient rad14Δ strains have elevated mutation rates that depend on Pol ζ. Rates are most strongly elevated for tandem base pair substitutions and clusters of multiple, closely spaced mutations. Both types of mutations depend on Pol ζ, but not on Pol η. Rates of each are further elevated in yeast strains bearing the rev3-979F allele. The results indicate that when Pol ζ performs mutagenic bypass of endogenous, helix-distorting lesions, it catalyzes a short track of processive, error-prone synthesis. We discuss the implications of this unique catalytic property of Pol ζ to its evolutionary conservation and possibly to multistage carcinogenesis.Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.

Polymerases:

Topics:

Fidelity

Status:

new topics/pols set partial results complete validated

Results:

No results available for this paper.

Entry validated by:

Using Polbase tables:

Sorting:

Tables may be sorted by clicking on any of the column titles. A second click reverses the sort order. <Ctrl> + click on the column titles to sort by more than one column (e.g. family then name).

Filtering:

It is also possible to filter the table by typing into the search box above the table. This will instantly hide lines from the table that do not contain your search text.