ArticleBMC biology2022
Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication.
Article in BMC biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Precise metabolomics identifies glycolysis-related pyruvate kinase M activity as regulator of the S-phase-specific radiation response in triple-negative breast cancer cells.Cell communication and signaling : CCS · 2026Article
- Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.FEMS microbiology reviews · 2026Review
- Review
- A novel effect of sulforaphane on promoting mouse granulosa cells proliferation via the NRF2-TKT pathway.Journal of advanced research · 2025Article
- Characterizing Common Factors Affecting Replication Initiation During HInternational journal of molecular sciences · 2025Article
- Article
- Moonlighting Proteins: Unveiling Their Multifunctionality in Metabolic Regulation and Drug Discovery.Current drug metabolism · 2025Review
- Nano-Se exhibits limited protective effect against heat stress induced poor breast muscle meat quality of broilers compared with other selenium sources.Journal of animal science and biotechnology · 2024Article
- Interaction networks of Escherichia coli replication proteins under different bacterial growth conditions.Scientific data · 2023Article
- Open Questions about the Roles of DnaA, Related Proteins, and Hyperstructure Dynamics in the Cell Cycle.Life (Basel, Switzerland) · 2023Review
- The metabolic control of DNA replication: mechanism and function.Open biology · 2023Review
- The Replicative DnaE Polymerase ofLife (Basel, Switzerland) · 2023Article
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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
backgroundIn all living organisms, DNA replication is exquisitely regulated in a wide range of growth conditions to achieve timely and accurate genome duplication prior to cell division. Failures in this regulation cause DNA damage with potentially disastrous consequences for cell viability and human health, including cancer. To cope with these threats, cells tightly control replication initiation using well-known mechanisms. They also couple DNA synthesis to nutrient richness and growth rate through a poorly understood process thought to involve central carbon metabolism. One such process may involve the cross-species conserved pyruvate kinase (PykA) which catalyzes the last reaction of glycolysis. Here we have investigated the role of PykA in regulating DNA replication in the model system Bacillus subtilis.
resultsOn analysing mutants of the catalytic (Cat) and C-terminal (PEPut) domains of B. subtilis PykA we found replication phenotypes in conditions where PykA is dispensable for growth. These phenotypes are independent from the effect of mutations on PykA catalytic activity and are not associated with significant changes in the metabolome. PEPut operates as a nutrient-dependent inhibitor of initiation while Cat acts as a stimulator of replication fork speed. Disruption of either PEPut or Cat replication function dramatically impacted the cell cycle and replication timing even in cells fully proficient in known replication control functions. In vitro, PykA modulates activities of enzymes essential for replication initiation and elongation via functional interactions. Additional experiments showed that PEPut regulates PykA activity and that Cat and PEPut determinants important for PykA catalytic activity regulation are also important for PykA-driven replication functions.
conclusionsWe infer from our findings that PykA typifies a new family of cross-species replication control regulators that drive the metabolic control of replication through a mechanism involving regulatory determinants of PykA catalytic activity. As disruption of PykA replication functions causes dramatic replication defects, we suggest that dysfunctions in this new family of universal replication regulators may pave the path to genetic instability and carcinogenesis.
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