title: Re-wiring of energy metabolism promotes viability during hyperreplication stress in E. coli.
abstract: 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.
authors.affiliation: Dept. of Biology, Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Godefroid
authors.identifier: 0000-0003-4792-1889
authors.initials: G
authors.lastname: Charbon
authors.affiliation: Dept. of Biology, Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christopher
authors.initials: C
authors.lastname: Campion
authors.affiliation: National Food Institute, Microbial Biotechnology and Biorefining, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Siu Hung Joshua
authors.identifier: 0000-0002-7707-656X
authors.initials: SH
authors.lastname: Chan
authors.affiliation: Dept. of Biology, Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Louise
authors.identifier: 0000-0002-5086-4582
authors.initials: L
authors.lastname: Bjørn
authors.affiliation: Laboratory of Clinical Pharmacology, Rigshospitalet, Section Q7642, Copenhagen Denmark and Department of Clinical Pharmacology, Bispebjerg Frederiksberg Hospitals, Copenhagen Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.affiliation: Dept. of Biology, Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Luís Cláudio Nascimento
authors.identifier: 0000-0002-4206-0904
authors.initials: LC
authors.lastname: da Silva
authors.affiliation: National Food Institute, Microbial Biotechnology and Biorefining, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Peter Ruhdal
authors.identifier: 0000-0003-2080-2070
authors.initials: PR
authors.lastname: Jensen
authors.affiliation: Dept. of Biology, Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.identifier: 0000-0002-0344-6417
authors.initials: A
authors.lastname: Løbner-Olesen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003573:Cytochrome b Group; D003580:Cytochromes / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D013312:Stress, Physiological
chemical_list: D001426:Bacterial Proteins; D003573:Cytochrome b Group; D003580:Cytochromes; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; D045222:Electron Transport Chain Complex Proteins; D029968:Escherichia coli Proteins; D010088:Oxidoreductases; C040077:cytochrome bd terminal oxidase complex, E coli