Coordination of chromosome replication and cell cycle progression in Caulobacter

Abstract

The Caulobacter cell cycle is driven by sequential regulators, starting with the expression of DnaA in G1 and ending with the expression of the CcrM DNA methyltransferase at the end of replication. DnaA both allows replisome formation and is a transcription factor for over 40 replication genes. The timing of dnaA transcription is dependent on the methylation state of its promoter, which in turn is dependent on restricting the synthesis of CcrM to the end of the cell cycle. Replication initiation starts on a fully methylated chromosome. The dnaA gene, positioned near the replication origin, is only read when its promoter is in the fully methylated state. When the replication fork passes the dnaA gene, the dnaA promoter becomes hemi‐methylated and thus inactivated. This methylation‐based regulation of dnaA transcription modulates the temporal levels of DnaA during the cell cycle, providing a ratchet mechanism to govern sequential regulator expression.The bacterial cell also uses spatial information to coordinate cell cycle events. In Caulobacter, a novel system couples the placement of the FtsZ cytokinetic ring to the initiation of chromosome replication and the bipolar positioning of the duplicated origin regions. A ParA‐like protein, MipZ, forms a complex with the ParB partitioning protein near the origin of replication and moves with the duplicated origin regions to the cell poles. MipZ directly interferes with FtsZ polymerization, thereby restricting FtsZ ring formation to mid‐cell, the region of lowest MipZ concentration. The cellular positioning of MipZ thus serves the duel function of positioning the FtsZ ring in‐between the two nascent sister nucleoids and delaying formation of the cell division apparatus until chromosome segregation has initiated.