The SOS and RpoS Regulons Contribute to Bacterial Cell Robustness to Genotoxic Stress by Synergistically Regulating DNA Polymerase Pol II

Abstract

Mitomycin C (MMC) is a genotoxic agent that induces DNA cross-links, DNA alkylation, and the production of reactive oxygen species (ROS). MMC induces the SOS response and RpoS regulons in Escherichia coli. SOS-encoded functions are required for DNA repair, whereas the RpoS regulon is typically induced by metabolic stresses that slow growth. Thus, induction of the RpoS regulon by MMC may be coincidental, because DNA damage slows growth; alternatively, the RpoS regulon may be an adaptive response contributing to cell survival. In this study, we show that the RpoS regulon is primarily induced by MMC-induced ROS production. We also show that RpoS regulon induction is required for the survival of MMC-treated growing cells. The major contributor to RpoS-dependent resistance to MMC treatment is DNA polymerase Pol II, which is encoded by the polB gene belonging to the SOS regulon. The observation that polB gene expression is controlled by the two major stress response regulons that are required to maximize survival and fitness further emphasizes the key role of this DNA polymerase as an important factor in genome stability.

Gamblers: an Antibiotic-induced Evolvable Cell Subpopulation Differentiated by Reactive-oxygen-induced General Stress Response

“…These data highlight the centrality of stress-response-control of mutagenesis, even ROS-induced mutagenesis, and identify ROS as signaling molecules in this regulation. The DNA crosslinking agent mitomycin C also induces ROS that induce the σ S response (Dapa et al, 2017), which might occur by similar mechanism with similar mutagenic consequences as shown here.…”

Evolving metabolism of 2,4‐dinitrotoluene triggers SOS‐independent diversification of host cells

“…As sketched in Fig. , ROS induces the RpoS regulon (Dapa et al, ), an event that bifurcates in two directions. First, it enhances expression of DNA polymerase IV (Pol IV) encoded by the dinB gene in a fashion that increases upon activation of the recA ‐mediated SOS response (Galhardo et al, ).…”

“…The role of other rpoS-dependent DNA polymerases (e.g. Pol II encoded by the polB gene; Dapa et al, 2017) was not explored in this work but may deserve further studies.…”

Qualitative and quantitative assessment of genotoxins usingSRRzlysis reporter under the control of a newly designed SOS responsive promoter inEscherichia coli

“…20 Mitomycin C (MMC) and methyl methanesulfonate (MMS) are direct-acting alkylating agents that may induce SOS response in E. coli through forming cross-links to adjacent guanines in DNA. 21,22 MMC may strongly induces the SOS response, while MMS showed lower mutagenic activities in the SOS/umu-test. 15,21,22 Azinphos-methyl is classied by the World Health Organization (WHO 2010) as groups 1 (acute toxicity) and 3 (environmental toxicity).…”

“…21,22 MMC may strongly induces the SOS response, while MMS showed lower mutagenic activities in the SOS/umu-test. 15,21,22 Azinphos-methyl is classied by the World Health Organization (WHO 2010) as groups 1 (acute toxicity) and 3 (environmental toxicity). Results indicated that the azinphos-methyl might induce mutation through frameshi mutation and pair base substitution.…”