ArticleNucleic acids research2018
Pyrophosphate hydrolysis is an intrinsic and critical step of the DNA synthesis reaction.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed.
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- Visualizing DNA polymerase ι catalyze Hoogsteen-directed DNA synthesis.Nature communications · 2025Article
- Single-cell transcriptome analyses reveal the mechanism of mitochondrial activity in erectile dysfunction.Sexual medicine · 2025Article
- Continuous Detection of Cobalt Ions and Pyrophosphates by NAC-CdTe Quantum Dots Fluorescence Probes.Journal of fluorescence · 2025Article
- Coordinated transcriptional response to environmental stress by a Synechococcus virus.The ISME journal · 2024Article
- Repair and tolerance of DNA damage at the replication fork: A structural perspective.Current opinion in structural biology · 2023Review
- Thumb-domain dynamics modulate the functional repertoire of DNA-Polymerase IV (DinB).Nucleic acids research · 2023Article
- Colorimetry-Based Phosphate Measurement for Polymerase Elongation.BioMed research international · 2023Article
- New insights into DNA polymerase mechanisms provided by time-lapse crystallography.Current opinion in structural biology · 2022Review
- Transient State Kinetics ofBiochemistry · 2022Article
- A prebiotic basis for ATP as the universal energy currency.PLoS biology · 2022Article
- Analysis and validation of silica-immobilised BST polymerase in loop-mediated isothermal amplification (LAMP) for malaria diagnosis.Analytical and bioanalytical chemistry · 2022Article
- Molecular Characterization of a DNA Polymerase fromInternational journal of molecular sciences · 2022Article
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
- Carbodiimide-Driven Dimerization and Self-Assembly of Artificial, Ribose-Based Amphiphiles.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Essential role of pyrophosphate homeostasis mediated by the pyrophosphate-dependent phosphofructokinase in Toxoplasma gondii.PLoS pathogens · 2022Article
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Abstract
DNA synthesis by DNA polymerases (dPols) is central to duplication and maintenance of the genome in all living organisms. dPols catalyze the formation of a phosphodiester bond between the incoming deoxynucleoside triphosphate and the terminal primer nucleotide with the release of a pyrophosphate (PPi) group. It is believed that formation of the phosphodiester bond is an endergonic reaction and PPi has to be hydrolyzed by accompanying pyrophosphatase enzymes to ensure that the free energy change of the DNA synthesis reaction is negative and it can proceed in the forward direction. The fact that DNA synthesis proceeds in vitro in the absence of pyrophosphatases represents a long-standing conundrum regarding the thermodynamics of the DNA synthesis reaction. Using time-resolved crystallography, we show that hydrolysis of PPi is an intrinsic and critical step of the DNA synthesis reaction catalyzed by dPols. The hydrolysis of PPi occurs after the formation of the phosphodiester bond and ensures that the DNA synthesis reaction is energetically favorable without the need for additional enzymes. Also, we observe that DNA synthesis is a two Mg2+ ion assisted stepwise associative SN2 reaction. Overall, this study provides deep temporal insight regarding the primary enzymatic reaction responsible for genome duplication.
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