The effect of oxidative metabolism on spontaneous Polζ-dependent translesion synthesis in Saccharomyces cerevisiae

Brenda K. Minesinger, Amy L. Abdulovic, Tingwei M. Ou, Sue Jinks-Robertson

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)226-234
Number of pages9
JournalDNA Repair
Volume5
Issue number2
DOIs
StatePublished - Feb 3 2006
Externally publishedYes

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Keywords

  • Oxidative damage
  • Polymerase zeta
  • Reactive oxygen species
  • Spontaneous DNA damage
  • Translesion synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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