Kim C. Quon

Cell Cycle Control by an Essential Bacterial Two-Component Signal Transduction Protein

Dividing cells must coordinate cell cycle events to ensure genetic stability. Here we identify an essential two-component signal transduction protein that controls multiple events in the Caulobacter cell cycle, including cell division, stalk synthesis, and cell cycle-specific transcription. This protein, CtrA, is homologous to response regulator transcription factors and controls transcription from a group of cell cycle-regulated promoters critical for DNA replication, DNA methylation, and flagellar biogenesis. CtrA activity in the cell cycle is controlled both transcriptionally and by phosphorylation. As purified CtrA binds an essential DNA sequence motif found within its target promoters, we propose that CtrA acts in a phosphorelay signal transduction system to control bacterial cell cycle events directly at the transcriptional level.

Cell type-specific phosphorylation and proteolysis of a transcriptional regulator controls the G1-to-S transition in a bacterial cell cycle.

The global transcriptional regulator CtrA controls multiple events in the Caulobacter cell cycle, including the initiation of DNA replication, DNA methylation, cell division, and flagellar biogenesis. CtrA is a member of the response regulator family of two component signal transduction systems and is activated by phosphorylation. We report here that this phosphorylation signal enters the cell cycle at mid S phase. In addition, CtrA function is modulated by temporally and spatially controlled proteolysis. When an active CtrA protein is present at the wrong time in the cell cycle, owing to expression of a mutant CtrA derivative that is active in the absence of phosphorylation and is not turned over during the cell cycle, the G1-to-S transition is blocked and the cell cycle aborts. Thus, both phosphorylation and proteolysis are critical determinants of bacterial cell cycle control in a manner that is analogous to the control of the eukaryotic cell cycle.

The control of temporal and spatial organization during the Caulobacter cell cycle

The Caulobacter cell cycle exhibits time-dependent expression of differentiation events. These include the morphological transition of a swarmer cell to a replication-competent stalked cell and the subsequent polarized distribution of specific gene products that results in an asymmetric predivisional cell. Cell division then yields a new swarmer cell and a stem-cell-like stalked cell. Two-component signal transduction proteins involved in cell cycle control and proteins required for cell division and flagellar biogenesis have been shown to be regulated temporally and spatially during the cell cycle. The mechanisms underlying this regulation include protein phosphorylation and proteolysis.