Acquisition of drug-resistance in microorganisms has been of great interest in research and medicine. When cells are under selective pressure, their growth is often arrested, however some cells will undergo adaptive mutagenesis, a process in which arrested cells develop a mutation that allows them to overcome the selective pressure and resume growth. During growth arrest, replication will not take place, but transcription continues to provide proteins required for cell survival, thus we are interested in the contribution of transcription in the mechanism of adaptive mutagenesis. Using the yeast Saccharomyces cerevisiae as a model system, we explored the interplay between transcription and DNA damage in initiating adaptive mutagenesis by generating a mutant cell line lacking Rad26, a protein required for transcription-coupled DNA repair (TCR). We knocked out Rad26, both alone and in conjunction with Ogg1, deletion of which increases the steady state levels of oxidative DNA damage. Preliminary results indicate that loss of Rad26 has little effect on adaptive mutagenesis in either a WT or ogg1Δ background. This data could suggest that the types of DNA damage that contribute to adaptive mutagenesis (for example, we see a significant increase in the adaptive mutation frequency of ogg1Δ over WT) are largely not subject to TCR. Alternatively, overlapping functions of Rad26 and other proteins involved in TCR may mean that additional genetic manipulations are required in order to fully elucidate a role for TCR in this process.

Elucidating the role of transcription in adaptive mutagenesis with rad26Δ cell lines of Saccharomyces cerevisiae

255th National Meeting (2018)

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