PT  - JOURNAL ARTICLE
AU  - Sharath Narayanan
AU  - Lokesh Kumar
AU  - Sunish Kumar Radhakrishnan
TI  - Sensory domain of the cell cycle kinase CckA in <em>Caulobacter crescentus</em> regulates the differential DNA binding activity of the master regulator CtrA
AID  - 10.1101/300178
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 300178
4099  - http://biorxiv.org/content/early/2018/04/14/300178.short
4100  - http://biorxiv.org/content/early/2018/04/14/300178.full
AB  - Sophisticated signaling mechanisms allow bacterial cells to cope with environmental and intracellular challenges. Activation of specific pathways facilitates the cells to overcome cellular damage and thereby warrant integrity. Here we demonstrate the pliability of the CckA-CtrA two component signaling system in the freshwater bacterium, Caulobacter crescentus. Our forward genetic screen to analyse suppressor mutations that can negate the chromosome segregation block induced by the topoisomerase IV inhibitor, NstA, yielded various point mutations in the cell cycle histidine kinase, CckA. Notably, we identified a point mutation in the PAS-B domain of CckA, which resulted in increased levels of phosphorylated CtrA (CtrA∼P), the master cell cycle regulator. Surprisingly, this increase in CtrA∼P levels did not translate into a genome-wide increase in the DNA occupancy of CtrA, but specifically enriched its affinity to the chromosomal origin of replication, Cori, and a very small sub-set of CtrA regulated promoters. We show that through this enhanced binding of CtrA to the Cori, cells are able to overcome the toxic defects rendered by stable NstA through a possible slow down in the chromosome cycle. Taken together, our work opens up an unexplored and intriguing aspect of the CckA-CtrA signal transduction pathway. The distinctive DNA binding nature of CtrA and its regulation by CckA might also be crucial for pathogenesis because of the highly conserved nature of CckA-CtrA pathway in alphaproteobacteria.