ArticleNature chemical biology2017
Modulating the DNA polymerase β reaction equilibrium to dissect the reverse reaction.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Semi-rational engineering of terminal deoxynucleotidyl transferase for high-efficiency enzymaticSynthetic and systems biotechnology · 2026Article
- Unveiling the Mechanism of Deprotonation and Proton Transfer of DNA Polymerase Catalysis via Single-Molecule Conductance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- An exonuclease-resistant chain-terminating nucleotide analogue targeting the SARS-CoV-2 replicase complex.Nucleic acids research · 2024Article
- Reclassification of family A DNA polymerases reveals novel functional subfamilies and distinctive structural features.Nucleic acids research · 2023Article
- Human Polβ Natural Polymorphic Variants G118V and R149I Affects Substate Binding and Catalysis.International journal of molecular sciences · 2023Article
- Polβ/XRCC1 heterodimerization dictates DNA damage recognition and basal Polβ protein levels without interfering with mouse viability or fertility.DNA repair · 2023Article
- Kinetics of elementary steps in loop-mediated isothermal amplification (LAMP) show that strand invasion during initiation is rate-limiting.Nucleic acids research · 2023Article
- New insights into DNA polymerase mechanisms provided by time-lapse crystallography.Current opinion in structural biology · 2022Review
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
- Interlocking activities of DNA polymerase β in the base excision repair pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.Nature communications · 2021Article
- Mechanism of Deoxyguanosine Diphosphate Insertion by Human DNA Polymerase β.Biochemistry · 2021Article
- Visualizing Rev1 catalyze protein-template DNA synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- DNA polymerase β: Closing the gap between structure and function.DNA repair · 2020Review
- History of DNA polymerase β X-ray crystallography.DNA repair · 2020Review
- Quaternary structural diversity in eukaryotic DNA polymerases: monomeric to multimeric form.Current genetics · 2020Review
- Article
- The nature of the DNA substrate influences pre-catalytic conformational changes of DNA polymerase β.The Journal of biological chemistry · 2018Article
- Pyrophosphate hydrolysis is an intrinsic and critical step of the DNA synthesis reaction.Nucleic acids research · 2018Article
- Mapping Functional Substrate-Enzyme Interactions in the pol β Active Site through Chemical Biology: Structural Responses to Acidity Modification of Incoming dNTPs.Biochemistry · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this reaction favors nucleotide incorporation, polymerases also catalyze a reverse reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates deoxynucleoside triphosphates. Because pyrophosphorolysis can influence polymerase fidelity and sensitivity to chain-terminating nucleosides, we analyzed pyrophosphorolysis with human DNA polymerase β and found the reaction to be inefficient. The lack of a thio-elemental effect indicated that this reaction was limited by a nonchemical step. Use of a pyrophosphate analog, in which the bridging oxygen is replaced with an imido group (PNP), increased the rate of the reverse reaction and displayed a large thio-elemental effect, indicating that chemistry was now rate determining. Time-lapse crystallography with PNP captured structures consistent with a chemical equilibrium favoring the reverse reaction. These results highlight the importance of the bridging atom between the β- and γ-phosphates of the incoming nucleotide in reaction chemistry, enzyme conformational changes, and overall reaction equilibrium.
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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.