Article ID Journal Published Year Pages File Type
1981519 DNA Repair 2006 9 Pages PDF
Abstract

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 Polζ, and provide a mutational signature for mutagenic Polζ-dependent activity. In the current study, we have found that a specific subset of the Polζ-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.

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Life Sciences Biochemistry, Genetics and Molecular Biology Biochemistry
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