In non-dividing cells, such as those subject to drug pressure, the influence of persistent DNA damage on transcription could affect cellular outcomes. Base damage can be bypassed by RNA polymerase, resulting in a pool of mutant mRNAs through transcriptional mutagenesis (TM), and potentially a population of mutant proteins that could alter the phenotype of the cell. We hypothesize that TM could be an important first step in acquiring drug resistance, as the mutant protein could allow cells to resume DNA replication and convert this damage to a permanent advantageous mutation, a process we call retromutagenesis. Using Saccharomyces cerevisiae as a model organism, we have established an experimental system to elucidate this process. Furthermore, we have begun to explore the effects of increasing steady state levels of DNA damage by either compromising repair pathways or inducing additional damage with UV-A irradiation.

Retromutagenesis: A novel approach to drug resistance in microorganisms

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.