DnaA regulates stationary phase-specific expression of a AAA family gene in Caulobacter crescentus.

In most eubacteria the initiator protein DnaA triggers chromosomal replication by forming an initiation complex at the origin of replication and also functions as a transcriptional regulator, coordinating gene expression with cell cycle progression. While DnaA-regulated genes are relatively well characterized in exponentially growing cells, its role in gene regulation during stationary phase remains insufficiently explored. Here, using an aquatic bacterium Caulobacter crescentus as a model, we show that C. crescentus DnaA (ccDnaA) acts as a repressor of the previously uncharacterized CCNA_00139 gene, which encodes a YifB family Mg chelatase-like AAA ATPase family protein of unknown function. Biochemical analyses reveal that ccDnaA forms multimers at this site, which may interfere with RNA polymerase access to the promoter by occupying overlapping binding sequences. Consistently, in exponentially growing C. crescentus cells, the CCNA_00139 promoter is repressed in a ccDnaA-dependent manner. Notably, when cells enter stationary phase, the CCNA_00139 promoter activity increases in parallel with ccDnaA clearance, supporting the idea that ccDnaA-mediated repression is relieved during this phase transition. Despite its regulated expression, deletion of CCNA_00139 did not result in any detectable growth, replication, or DNA damage sensitivity phenotypes under the tested laboratory conditions, suggesting a possible role under specific environmental conditions. Given this phase-dependent transcriptional switch may, in principle, apply to other uncharacterized ccDnaA-repressed genes, we infer that CCNA_00139, along with other such genes, form a regulatory network that supports quorum sensing or adaptation to growth phase transitions. We believe that these findings would offer new insight into the potential role of bacterial DnaA in regulating gene expression in dormant or non-replicating cells across diverse bacterial species.