Proliferating cells must coordinate central metabolism with the cell cycle. How central energy metabolism regulates bacterial cell cycle functions is not well understood. Our forward genetic selection unearthed the Krebs cycle enzyme citrate synthase (CitA) as a checkpoint regulator controlling the G1→S transition in the polarized alpha-proteobacterium Caulobacter crescentus, a model for cell cycle regulation and asymmetric cell division. We find that loss of CitA promotes the accumulation of active CtrA, an essential cell cycle transcriptional regulator that maintains cells in G1-phase, provided that the (p)ppGpp alarmone is present. The enzymatic activity of CitA is dispensable for CtrA control and functional citrate synthase paralogs cannot replace CitA in promoting S-phase entry. Our evidence suggests that CitA was appropriated specifically to function as a moonlighting enzyme to link central energy metabolism with S-phase entry. Control of the G1-phase with a central metabolic enzyme may be a common mechanism of cellular regulation.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Tn-seq and metabolomics data.
Polymerase occupancy (ChIP-Seq) in WT and mutants of Caulobacter crescentus NA1000NCBI Gene Expression Omnibus, GSE144533.
Examination of 5 transcripton factor binding in two different speciesNCBI Gene Expression Omnibus, GSE52849.
- Patrick H Viollier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Bavesh D Kana, University of the Witwatersrand, South Africa
© 2020, Bergé et al.
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