Reactive oxygen species (ROS) are byproducts of normal cellular metabolism. However, their levels can be increased by external factors such as UV-A light or hydrogen peroxide, causing oxidative stress. These ROS can damage the DNA, and if the damage is left unrepaired, it can lead to permanent mutations that may affect the characteristics of the cell. Our laboratory is interested in the mechanism by which non-dividing cells acquire mutations in response to selective pressure that inhibits their growth, a process known as adaptive mutagenesis. Previous work has shown that compromising the repair of oxidative DNA damage (ogg1Δ cells) or the proofreading capacity of the RNA polymerase during transcription (dst1Δ cells) increases the frequency of adaptive mutagenesis. Additional studies have also indicated that dst1Δ cells are more sensitive to oxidative stress than their WT counterparts. In this study, we assessed the effects of H2O2-induced oxidative stress on cells lacking dst1, both alone and in conjunction with ogg1Δ, with respect to cell survival and mutagenesis. Cells lacking dst1 showed a significant decrease in survival relative to their WT or ogg1Δ counterparts following exposure to H2O2, but this effect was modest. With respect to mutagenesis, oxidative stress increased the mutation rates in all cell lines. Interestingly, the increase observed in the dst1Δogg1Δ was higher than in the ogg1Δ cells alone, suggesting a possible role for transcriptional proofreading in combating the accumulation of mutations following oxidative damage.

Effects of oxidative DNA damage on survival and mutagenesis in Saccharomyces cerevisiae

255th National Meeting (2018)

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