In non-dividing cells, the influence of persistent DNA damage on transcription could affect cellular outcomes. RNA polymerases can bypass several types of frequently occurring base damage in a mutagenic fashion, generating a pool of mutant mRNAs in a process known as transcriptional mutagenesis (TM).  The mutant mRNA could be translated into a population of mutant proteins with the ability to alter the phenotype of the cell.  We predict that if the mutant protein generated allows the cell to escape growth constraints, a round of DNA replication will ensue.  This would cause the lesion that led to the advantageous mutant protein via TM to be encountered by the replication machinery, leading to a permanent DNA sequence change.  Initial experiments using the model organism Saccharomyces cerevisiae aim to establish an experimental system to ascertain the frequency and molecular mechanism with which this process of retromutagenesis is likely to occur.

Elucidating the role of transcriptional mutagenesis in the acquisition of drug resistance

243rd National Meeting (2012)

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