Re-wiring of energy metabolism promotes viability during hyperreplication stress in E. coli

• DOI: 10.1371/journal.pgen.1006590
• Publication Date: 2017-01-27T18:25:05Z
• Authors: Godefroid Charbon; Christopher Campion; Siu Hung Joshua Chan; Louise Bjørn; Allan Weimann; Luís Cláudio Nasc...; Peter Ruhdal Jensen; Anders Løbner-Olesen
• Keywords: DNA Replication; 0301 basic medicine; Escherichia coli Proteins; Replication Origin; QH426-470; Cytochrome b Group; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; Bacterial Proteins; Electron Transport Chain Complex Proteins; Stress, Physiological; Genetics; Escherichia coli; Cytochromes; Energy Metabolism; Oxidoreductases; Research Article

Chromosome replication in Escherichia coli is initiated by DnaA. DnaA binds ATP which is essential for formation of a DnaA-oriC nucleoprotein complex that promotes strand opening, helicase loading and replisome assembly. Following initiation, DnaAATP is converted to DnaAADP primarily by the Regulatory Inactivation of DnaA process (RIDA). In RIDA deficient cells, DnaAATP accumulates leading to uncontrolled initiation of replication and cell death by accumulation of DNA strand breaks. Mutations that suppress RIDA deficiency either dampen overinitiation or permit growth despite overinitiation. We characterize mutations of the last group that have in common that distinct metabolic routes are rewired resulting in the redirection of electron flow towards the cytochrome bd-1. We propose a model where cytochrome bd-1 lowers the formation of reactive oxygen species and hence oxidative damage to the DNA in general. This increases the processivity of replication forks generated by overinitiation to a level that sustains viability.