Principal Investigator Alan Grossman
We have characterized several aspects of transcriptional regulation in response to perturbations in DNA replication. Perturbations in replication inhibit the initiation of sporulation in B. subtilis and also inhibit cell division in many types of bacteria.
We characterized the transcriptional response to perturbations in DNA replication caused by DNA damage and disruptions to the replication complex. Upon inhibition of replication (either initiation or elongation), expression of many genes changes. A significant part of this response is mediated by the conserved replication initiation protein and transcription factor DnaA. DnaA represses expression of some genes and activates others. This is independent of the well characterized RecA-mediated SOS response. We found that the DnaA-mediated response activates an inhibitor of sporulation, and also represses transcription of an essential cell division gene (whose product is unstable), thereby inhibiting sporulation and cell division. Furthermore, many of the genes apparently controlled directly by DnaA are conserved and have putative DnaA binding sites in their regulatory regions in other bacteria, indicating that this response is widespread.