Abstract
To maintain genome integrity, organisms employ DNA damage response, the underlying principles of which are conserved from bacteria to humans. The bacterial small RNA OxyS of Escherichia coli is induced upon oxidative stress and has been implicated in protecting cells from DNA damage; however, the mechanism by which OxyS confers genome stability remained unknown. Here, we revealed an OxyS‐induced molecular checkpoint relay, leading to temporary cell cycle arrest to allow damage repair. By repressing the expression of the essential transcription termination factor nusG, OxyS enables read‐through transcription into a cryptic prophage encoding kilR. The KilR protein interferes with the function of the major cell division protein FtsZ, thus imposing growth arrest. This transient growth inhibition facilitates DNA damage repair, enabling cellular recovery, thereby increasing viability following stress. The OxyS‐mediated growth arrest represents a novel tier of defense, introducing a new regulatory concept into bacterial stress response.
Highlights
The oxidative stress-induced OxyS small RNA was one of the first characterized sRNAs (Altuvia et al, 1997)
To eliminate mutations rendering OxyS completely inactive, for example, by decreasing sRNA stability, we focused on mutants that are no longer toxic, but capable of repressing fhlA-lacZ, a previously characterized target of OxyS (Argaman & Altuvia, 2000)
Northern blots showed that the RNA levels of the suppressor OxyS mutants were comparable to wild-type OxyS (Fig 2B), and functional assays showed that OxyS mutants repressed the translation of fhlA-lacZ (Appendix Fig S1B), indicating that the OxyS mutants were active regulators, though not toxic
Summary
The oxidative stress-induced OxyS small RNA (sRNA) was one of the first characterized sRNAs (Altuvia et al, 1997). Whereas negative regulation of rpoS (stationary-phase sigma factor) appears to be indirect, that is, via titration of Hfq, regulation of fhlA and flhDC by OxyS results from direct base pairing with their mRNAs (Altuvia et al, 1998; Zhang et al, 1998; Argaman & Altuvia, 2000; Moon & Gottesman, 2011; De Lay & Gottesman, 2012) Despite these findings, an intriguing aspect of OxyS remained enigmatic ever since its discovery; the RNA has been proposed to play a key role in protecting cells against the damaging effects of spontaneous and induced mutagenesis (Altuvia et al, 1997). We propose that the transient inhibition of cell division induced by OxyS facilitates DNA repair and recovery from oxidative stress
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