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bioRxiv · 10.1101/2021.10.23.465540

Fine-tuning of RecBCD expression by post-transcriptional regulation is required for optimal DNA repair in Escherichia coli

Kalita, I.·Iosub, I. A.·Granneman, S.·El Karoui, M.
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Abstract

All living organisms have developed strategies to respond to chromosomal damage and preserve genome integrity. One such response is the repair of DNA double-strand breaks (DSBs), one of the most toxic forms of DNA lesions. In Escherichia coli, DSBs are repaired via RecBCD-dependent homologous recombination. RecBCD is essential for accurate chromosome maintenance, but its over-expression can lead to reduced DNA repair ability. This apparent paradox suggests that RecBCD copy numbers may need to be tightly controlled within an optimal range. Using single-molecule fluorescence microscopy, we have established that RecB is present in very low abundance at mRNA and protein levels. RecB transcription shows high fluctuations, yet cell-to-cell protein variability remains remarkably low. Here, we show that the post-transcriptional regulator Hfq binds to recB mRNA and down-regulates RecB protein translation in vivo. Furthermore, specific disruption of the Hfq-binding site leads to more efficient translation of recB mRNAs. In addition, we observe a less effective reduction of RecB protein fluctuations in the absence of Hfq. This fine-tuning Hfq-mediated mechanism might have the underlying physiological function of maintaining RecB protein levels within an optimal range.

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Kalita, I., Iosub, I. A., Granneman, S., El Karoui, M.. 2021-10-24. Fine-tuning of RecBCD expression by post-transcriptional regulation is required for optimal DNA repair in Escherichia coli. https://doi.org/10.1101/2021.10.23.465540

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