Computational modeling of unphosphorylated CtrA:Cori binding in the Caulobacter cell cycle

In the alphaproteobacterium, Caulobacter crescentus, phosphorylated CtrA (CtrA similar to P), a master regulatory protein, binds directly to the chromosome origin (Cori) to inhibit DNA replication. Using a mathematical model of CtrA binding at Cori site [d], we provide computational evidence that CtrA(U) can disc ace CtrA similar to P from Cori at the G1-S transition. Investigation of this interaction within a detailed model of the C. crescentus cell cycle suggests that CckA phosphatase may clear Cori of CtrA similar to P by altering the [CtrA(U)]/[CtrA similar to P] ratio rather than by completely depleting CtrA similar to P. Model analysis reveals that the mechanism allows for a speedier transition into S phase, stabilizes the timing of chromosome replication under fluctuating rates of CtrA proteolysis, and may contribute to the viability of numerous mutant strains. Overall, these results suggest that CtrA(U) enhances the robustness of chromosome replication. More generally, our proposed regulation of CtrA:Cori dynamics may represent a novel motif for molecular signaling in cell physiology.