Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA
The synthesis and the degradation of DnaA are both subject to control mechanisms that respond to environmental changes. Changes in nutrient availability modulate the rate of DnaA synthesis by a mechanism involving the 5'UTR. Changes in the global protein folding state impact the rate of DnaA degradation by the protease Lon. During exponential growth high levels of nutrients promote translation of DnaA. Although DnaA is constantly degraded, the rate of synthesis is high enough to allow for the accumulation of DnaA and DNA replication initiation. In starvation and stationary phase conditions lower amounts of nutrients cause the translation rate of DnaA to decrease. Because DnaA degradation continues at the same rate as in exponential phase, DnaA is rapidly cleared leading to a cessation of DNA replication. In proteotoxic stress conditions, for example chaperone depletion or thermal stress, nutrients are still available and drive DnaA synthesis. However, Lon-mediated DnaA degradation is stimulated in these conditions leading to the clearance of DnaA and a G1-arrest .