ArticleBiophysical journal2017
Switching between Exonucleolysis and Replication by T7 DNA Polymerase Ensures High Fidelity.
Article in Biophysical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Translesion DNA synthesis on pyrimidine dimers by plant organellar DNA polymerases is metal-dependent.Nucleic acids research · 2026Article
- DNA polymerase actively and sequentially displaces single-stranded DNA-binding proteins.Nature communications · 2025Article
- Measuring molecular forces inside living cells using magnetic tweezers.Biophysical reviews · 2025Review
- The POLγ Y951N patient mutation disrupts the switch between DNA synthesis and proofreading, triggering mitochondrial DNA instability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DNA Polymerase Locks Replication Fork Under Stress.bioRxiv : the preprint server for biology · 2024Article
- Mapping fast DNA polymerase exchange during replication.Nature communications · 2024Article
- Life under tension: the relevance of force on biological polymers.Biophysics reports · 2024Article
- Polγ coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.Nature structural & molecular biology · 2023Article
- Calculating the force-dependent unbinding rate of biological macromolecular bonds from force-ramp optical trapping assays.Scientific reports · 2022Article
- Conformational Dynamics of DNA Polymerases Revealed at the Single-Molecule Level.Frontiers in molecular biosciences · 2022Review
- The nucleotide addition cycle of the SARS-CoV-2 polymerase.Cell reports · 2021Article
- Checkpoint-mediated DNA polymerase ε exonuclease activity curbing counteracts resection-driven fork collapse.Molecular cell · 2021Article
- The nucleotide addition cycle of the SARS-CoV-2 polymerase.bioRxiv : the preprint server for biology · 2021Article
- DNA replication:Computational and structural biotechnology journal · 2021Review
- DNA replication machinery: Insights fromComputational and structural biotechnology journal · 2021Review
- Excessive excision of correct nucleotides during DNA synthesis explained by replication hurdles.The EMBO journal · 2020Article
- Replicative DNA polymerases promote active displacement of SSB proteins during lagging strand synthesis.Nucleic acids research · 2019Article
- Mass-spectrometry analysis of modifications at DNA termini induced by DNA polymerases.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA polymerase catalyzes the accurate transfer of genetic information from one generation to the next, and thus it is vitally important for replication to be faithful. DNA polymerase fulfills the strict requirements for fidelity by a combination of mechanisms: 1) high selectivity for correct nucleotide incorporation, 2) a slowing down of the replication rate after misincorporation, and 3) proofreading by excision of misincorporated bases. To elucidate the kinetic interplay between replication and proofreading, we used high-resolution optical tweezers to probe how DNA-duplex stability affects replication by bacteriophage T7 DNA polymerase. Our data show highly irregular replication dynamics, with frequent pauses and direction reversals as the polymerase cycles through the states that govern the mechanochemistry behind high-fidelity T7 DNA replication. We constructed a kinetic model that incorporates both existing biochemical data and the, to our knowledge, novel states we observed. We fit the model directly to the acquired pause-time and run-time distributions. Our findings indicate that the main pathway for error correction is DNA polymerase dissociation-mediated DNA transfer, followed by biased binding into the exonuclease active site. The number of bases removed by this proofreading mechanism is much larger than the number of erroneous bases that would be expected to be incorporated, ensuring a high-fidelity replication of the bacteriophage T7 genome.
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