Biology

Dr. Sunish Radhakrishnan
IISER, Thiruvananthapuram

Topoisomerase IV, an essential factor during chromosome segregation in bacteria, decatenates the catenated circular chromosomes at the end of each replication cycle. It has been a long-standing question as to how the decatenating activity of the topoisomerase IV is regulated during the early stages of cell cycle, despite the topoisomerase IV being in association with the chromosome. Through forward genetics, we have identified a novel cell cycle regulated protein, NstA, as a negative switch of the decatenation activity of topoisomerase IV, during the early stages of cell cycle in the dimorphic bacterium, Caulobacter crescentus . The presence of NstA, during cell cycle, is tightly controlled at the level of transcription and protein abundance. Interestingly the activity of NstA itself is by dimerization through intermolecular cysteine disulfides. Most importantly, we uncover a dynamic oscillation of the cytoplasmic redox during cell cycle, which correlates with and controls the activity of NstA on topoisomerase IV, and is vital for the cell cycle progression. Thus, we propose that predetermined dynamic intracellular redox fluctuations regulate bacterial cell cycle progression and development.