Transcriptional regulation in response to stressful DNA replication

Presenter: Kelly McKnight, Graduate Student

The regulation of gene function in response to stressful conditions or different cell cycle stages is critical for cell survival and one major regulation is to increase or decrease gene transcription. During stressful DNA replication, the S-phase checkpoint activates transcription of repair genes and delays cell cycle progression; however the direct relationship between these events remains unclear. We have found that after treating yeast cells with the DNA synthesis inhibitor hydroxyurea, transcription of the ASE1 gene can start within the coding region through intragenic transcription to produce smaller mRNAs. This intragenic transcription depends on the S-phase checkpoint and produces smaller protein isoforms that likely act in a dominant negative manner. Therefore, intragenic transcription may be a vital uncharacterized response to stressful DNA replication and we are currently using next generation sequencing to identify other intragenic transcripts.