ArticleNature communications2020
Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path.
Article in Nature communications, 2020. 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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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
31 citing papers in PubMed.
- Conjugation as an evolutionary bottleneck in antimicrobial resistance spread.Frontiers in microbiology · 2026Review
- An efficient computational chemistry approach to generating negative data for drug discovery pipeline validation.Frontiers in bioinformatics · 2026Article
- The proofreading mechanism of the human leading-strand DNA polymerase ε holoenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Egress-enhancing mutation reveals the inefficiency of non-enveloped virus cell exit.PLoS biology · 2025Article
- Comparative analysis of gut microbiota in free range and house fed yaks from Linzhou County.Scientific reports · 2025Article
- 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
- Molecular model of TFIIH recruitment to the transcription-coupled repair machinery.Nature communications · 2025Article
- Getting the Right Clones in an Automated Manner: An Alternative to Sophisticated Colony-Picking Robotics.Bioengineering (Basel, Switzerland) · 2024Article
- Mapping fast DNA polymerase exchange during replication.Nature communications · 2024Article
- Escherichia coli DNA replication: the old model organism still holds many surprises.FEMS microbiology reviews · 2024Review
- Mutational Signatures in Wild Type Escherichia coli Strains Reveal Predominance of DNA Polymerase Errors.Genome biology and evolution · 2024Article
- High-fidelity, hyper-accurate, and evolved mutants rewire atomic-level communication in CRISPR-Cas9.Science advances · 2024Article
- New design strategies for ultra-specific CRISPR-Cas13a-based RNA detection with single-nucleotide mismatch sensitivity.Nucleic acids research · 2024Article
- Unveiling the RNA-mediated allosteric activation discloses functional hotspots in CRISPR-Cas13a.Nucleic acids research · 2024Article
- Human DNA Mutations and their Impact on Genetic Disorders.Recent patents on biotechnology · 2024Review
- Structural basis for DNA proofreading.Nature communications · 2023Article
- Molecular basis for proofreading by the unique exonuclease domain of Family-D DNA polymerases.Nature communications · 2023Article
- Polγ coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.Nature structural & molecular biology · 2023Article
- Machines on Genes through the Computational Microscope.Journal of chemical theory and computation · 2023Review
- The SARS-CoV-2 Hydra, a tiny monster from the 21st century: Thermodynamics of the BA.5.2 and BF.7 variants.Microbial risk analysis · 2023Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Proofreading by replicative DNA polymerases is a fundamental mechanism ensuring DNA replication fidelity. In proofreading, mis-incorporated nucleotides are excised through the 3'-5' exonuclease activity of the DNA polymerase holoenzyme. The exonuclease site is distal from the polymerization site, imposing stringent structural and kinetic requirements for efficient primer strand transfer. Yet, the molecular mechanism of this transfer is not known. Here we employ molecular simulations using recent cryo-EM structures and biochemical analyses to delineate an optimal free energy path connecting the polymerization and exonuclease states of E. coli replicative DNA polymerase Pol III. We identify structures for all intermediates, in which the transitioning primer strand is stabilized by conserved Pol III residues along the fingers, thumb and exonuclease domains. We demonstrate switching kinetics on a tens of milliseconds timescale and unveil a complete pol-to-exo switching mechanism, validated by targeted mutational experiments.
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Registered trials
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