Sensory domain of the cell cycle kinase CckA regulates the differential DNA binding of the master regulator CtrA in Caulobacter crescentus

Publication date: Available online 31 August 2018Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Sharath Narayanan, Lokesh Kumar, Sunish Kumar RadhakrishnanAbstractSophisticated signaling mechanisms allow bacterial cells to cope with environmental and intracellular challenges. Activation of specific pathways ameliorates these challenges and thereby warrants 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 analyze 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 for the chromosomal origin of replication, Cori, and for 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 replication cycle. Taken together, our work opens up an unexplored and intriguing aspect of the CckA-CtrA sign...
Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - Category: Genetics & Stem Cells Source Type: research