ArticleNature2015
Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed, 191 citations in OpenAlex.
- Cyclic di-GMP directly reprograms the multidrug resistance machinery via UspG-mediated sequestration of RamR in Klebsiella.PLoS pathogens · 2026Article
- Research on the Potential Mechanism of Guanine Nucleotides Enhancing the Tolerance ofFoods (Basel, Switzerland) · 2026Article
- Lifestyle-dependent evolution and CtrA-mediated lifestyle transitions shape phage resistance in marine Roseobacter.Nature communications · 2026Article
- Phosphodiesterase BpdE suppress bacterial proliferation by regulatingFrontiers in microbiology · 2026Article
- Dynamic Executors of Bacterial Signals: Functional Versatility and Regulatory Networks of c-di-GMP Effectors.Biomolecules · 2025Review
- Disrupting NtrC function reveals unexpected robustness in a central cell cycle regulatory network.mBio · 2025Article
- Oxidative Activation of the Heme Nitric Oxide/Oxygen-Binding Protein (H-NOX) fromBiochemistry · 2025Article
- Crosstalk between cyclic-di-guanosine monophosphate and the sensor kinase MtrB regulates MtrA-dependent genes, bacterial growth, biofilm formation and lysosomal trafficking ofMicrobiology (Reading, England) · 2025Article
- Article
- TheJournal of bacteriology · 2024Article
- A genetically encoded biosensor to monitor dynamic changes of c-di-GMP with high temporal resolution.Nature communications · 2024Article
- Review
- Phosphatase to kinase switch of a critical enzyme contributes to timing of cell differentiation.mBio · 2024Article
- Influence of the Heme Nitric Oxide/Oxygen Binding Protein (H-NOX) on Cell Cycle Regulation in Caulobacter crescentus.Molecular & cellular proteomics : MCP · 2023Article
- Phosphate starvation decouples cell differentiation from DNA replication control in the dimorphic bacterium Caulobacter crescentus.PLoS genetics · 2023Article
- Functional diversity of c-di-GMP receptors in prokaryotic and eukaryotic systems.Cell communication and signaling : CCS · 2023Review
- TheAnnual review of microbiology · 2023Review
- Gas and light: triggers of c-di-GMP-mediated regulation.FEMS microbiology reviews · 2023Review
- Article
- Structural features discriminating hybrid histidine kinase Rec domains from response regulator homologs.Nature communications · 2023Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fundamental to all living organisms is the capacity to coordinate cell division and cell differentiation to generate appropriate numbers of specialized cells. Whereas eukaryotes use cyclins and cyclin-dependent kinases to balance division with cell fate decisions, equivalent regulatory systems have not been described in bacteria. Moreover, the mechanisms used by bacteria to tune division in line with developmental programs are poorly understood. Here we show that Caulobacter crescentus, a bacterium with an asymmetric division cycle, uses oscillating levels of the second messenger cyclic diguanylate (c-di-GMP) to drive its cell cycle. We demonstrate that c-di-GMP directly binds to the essential cell cycle kinase CckA to inhibit kinase activity and stimulate phosphatase activity. An upshift of c-di-GMP during the G1-S transition switches CckA from the kinase to the phosphatase mode, thereby allowing replication initiation and cell cycle progression. Finally, we show that during division, c-di-GMP imposes spatial control on CckA to install the replication asymmetry of future daughter cells. These studies reveal c-di-GMP to be a cyclin-like molecule in bacteria that coordinates chromosome replication with cell morphogenesis in Caulobacter. The observation that c-di-GMP-mediated control is conserved in the plant pathogen Agrobacterium tumefaciens suggests a general mechanism through which this global regulator of bacterial virulence and persistence coordinates behaviour and cell proliferation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.