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.
Minesinger
Brenda K
BK
Biochemistry, Cell and Developmental Biology Program of the Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA.
Abdulovic
Amy L
AL
Ou
Tingwei M
TM
Jinks-Robertson
Sue
S
D000483:Alleles; D001483:Base Sequence; D003470:Culture Media; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D016368:Frameshift Mutation; D015966:Gene Expression Regulation, Fungal; D015751:Genes, pol; D005838:Genotype; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D003470:Culture Media; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C425929:DNA polymerase zeta; D004259:DNA-Directed DNA Polymerase; D010100:Oxygen