Nutritional control of bacterial DNA replication

Abstract

All cells must ensure precise regulation of DNA replication initiation in coordination with growth rate and in response to nutrient availability. According to a long-standing model, DNA replication initiation is tightly coupled to cell mass increase in bacteria. Despite controversies regarding this model, recent studies have provided additional support of this idea. The exact molecular mechanisms linking cell growth with DNA replication under different nutrient conditions remain elusive. However, recent studies in Caulobacter crescentus and Escherichia coli have provided insights into the regulation of DNA replication initiation in response to starvation. These mechanisms include the starvation-dependent regulation of DnaA abundance as well as mechanisms involving the small signaling molecule (p)ppGpp. In this review, we discuss these mechanisms in the context of previous findings. We highlight species-dependent similarities and differences and consider the precise growth conditions, in which the different mechanisms are active.