The effect of oxidative metabolism on spontaneous Pol zeta-dependent translesion synthesis in Saccharomyces cerevisiae.
DNA lesions can stall or block high-fidelity polymerases, thus inhibiting replication. To bypass such lesions, low-fidelity translesion synthesis (TLS) polymerases can be used to insert a nucleotide across from the lesion or extend from a lesion:base mispair. When DNA repair is compromised in Saccharomyces cerevisiae, spontaneous DNA lesions can lead to a novel mutational event in which a frameshift is accompanied by one or more base pair substitutions. These "complex frameshifts" are dependent upon the TLS polymerase Pol zeta, and provide a mutational signature for mutagenic Pol zeta-dependent activity. In the current study, we have found that a specific subset of the Pol zeta-dependent mutational events requires oxidative metabolism. These results suggest that translesion bypass of spontaneously oxidized DNA bases can be a significant source of mutagenesis in repair compromised cells.
Duke Scholars
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Reactive Oxygen Species
- Oxygen
- Mutation
- Mutagenesis
- Molecular Sequence Data
- Models, Statistical
- Models, Genetic
- Genotype
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Reactive Oxygen Species
- Oxygen
- Mutation
- Mutagenesis
- Molecular Sequence Data
- Models, Statistical
- Models, Genetic
- Genotype