Stress, Checkpoints, and Genome Stability: Cell Division Control

We are interested in understanding how cells sense and respond to changes in their environment. In particular, we focus on how Caulobacter cells respond to DNA damage. We have recently begun mapping the mechanisms by which cells sense DNA damage and respond by halting cell cycle progression and repairing their DNA. Our results thus far indicate that Caulobacter cells simultaneously up-regulate the genes required for physical repair of damaged DNA and down-regulate the master cell cycle regulator CtrA. The latter involves an unknown, post-translational mechanism which we are actively pursuing. In addition, we have recently identified the first bona fide checkpoint system in Caulobacter. This checkpoint is activated after DNA damage and helps halt the cell cycle by inhibiting chromosome segregation enzymes such as topo IV and gyrase. The precise mechanism by which this checkpoint acts is still being investigated.