A starvation-triggered AAA+ ATPase halts chromosome replication progression by disassembling the bacterial DNA sliding clamp

Abstract

To maintain genomic integrity, cells should modulate replication of their genetic material in response to nutrient availability, especially when nutrients become scarce. However, mechanisms regulating the progression of DNA replication when bacterial cells encounter starvation remain largely unclear. Herein, we identify the role of IncA, an AAA+ ATPase, in inhibiting the progression of chromosome replication in nutrient-starved cells of Caulobacter crescentus. We show that the starvation-induced alarmone (p)ppGpp enhances IncA production in the stationary phase cells. At the mechanistic level, we demonstrate that IncA directly interacts with the β-sliding clamp protein DnaN and delocalizes DnaN from the replisome, thereby stalling the progression of DNA replication. Furthermore, we reveal the requirement of the ATPase activity of IncA for disassembling DnaN. Remarkably, we demonstrate that the IncA homolog from E. coli is capable of delocalizing DnaN to inhibit DNA replication in Caulobacter. We propose that IncA homologs serve a stress-dependent role in inhibiting DNA replication across diverse domains of life.