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

Godefroid Charbon, Christopher Campion, Siu Hung Joshua Chan, Louise Bjørn, Allan Weimann, Luis da Silva, Peter Ruhdal Jensen, Anders Løbner-Olesen

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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.
Original languageEnglish
Article numbere1006590
JournalP L o S Genetics
Volume13
Issue number1
Number of pages26
ISSN1553-7390
DOIs
Publication statusPublished - 2017

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