ArticleJournal of the American Chemical Society2013
DNA mismatch synthesis complexes provide insights into base selectivity of a B family DNA polymerase.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- The A, B, C, D's of replicative DNA polymerase fidelity: utilizing high-throughput single-molecule sequencing to understand the molecular basis for DNA polymerase accuracy.Nucleic acids research · 2025Article
- 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
- Structural basis of error-prone DNA synthesis by DNA polymerase θ.Nature communications · 2025Article
- Insights into the A-C Mismatch Conformational Ensemble in Duplex DNA and its Role in Genetic Processes through a Structure-based Review.Journal of molecular biology · 2024Review
- Polγ coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.Nature structural & molecular biology · 2023Article
- In crystallo observation of three metal ion promoted DNA polymerase misincorporation.Nature communications · 2022Article
- Structural and functional insight into mismatch extension by human DNA polymerase α.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Twisting and swiveling domain motions in Cas9 to recognize target DNA duplexes, make double-strand breaks, and release cleaved duplexes.Frontiers in molecular biosciences · 2022Review
- Two-Metal-Ion Catalysis: Inhibition of DNA Polymerase Activity by a Third Divalent Metal Ion.Frontiers in molecular biosciences · 2022Review
- Structure of New Binary and Ternary DNA Polymerase Complexes From Bacteriophage RB69.Frontiers in molecular biosciences · 2021Article
- Environmental Effects on Guanine-Thymine Mispair Tautomerization Explored with Quantum Mechanical/Molecular Mechanical Free Energy Simulations.Journal of the American Chemical Society · 2020Article
- A polar filter in DNA polymerases prevents ribonucleotide incorporation.Nucleic acids research · 2019Article
- Engineering Polymerases for New Functions.Trends in biotechnology · 2019Review
- Structural and Kinetic Studies of the Effect of Guanine N7 Alkylation and Metal Cofactors on DNA Replication.Biochemistry · 2018Article
- Insights into the effect of minor groove interactions and metal cofactors on mutagenic replication by human DNA polymerase β.The Biochemical journal · 2018Article
- A DNA structural alphabet provides new insight into DNA flexibility.Acta crystallographica. Section D, Structural biology · 2018Article
- Article
- Different Divalent Cations Alter the Kinetics and Fidelity of DNA Polymerases.The Journal of biological chemistry · 2016Review
- Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Human DNA Polymerase ν Catalyzes Correct and Incorrect DNA Synthesis with High Catalytic Efficiency.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Current hypotheses that attempt to rationalize the high degree of base selectivity exhibited by replicative DNA polymerases (pols) concur that ternary complexes formed with incorrect dNTPs are destabilized. Knowing what accounts for this destabilization is likely to be the key to understanding base discrimination. To address this issue, we have determined crystal structures of ternary complexes with all 12 mismatches using an engineered RB69 pol quadruple mutant (qm, L415A/L561A/S565G/Y567A) that enabled us to capture nascent mispaired dNTPs. These structures show that mismatches in the nascent base-pair binding pocket (NBP) of the qm pol differ markedly from mismatches embedded in binary pol-DNA complexes. Surprisingly, only 3 of 12 mismatches clash with the NBP when they are modeled into the wild-type (wt) pol. The remaining can fit into a wt pol ternary complex but deviate from normal Watson-Crick base-pairs. Repositioning of the templating nucleotide residue and the enlarged NBP in qm ternary complex play important roles in accommodating incorrect incoming dNTPs. From these structures, we propose additional reasons as to why incorrect dNTPs are incorporated so inefficiently by wt RB69 pol: (i) steric clashes with side chains in the NBP after Fingers closing; (ii) weak interactions or large gaps between the incoming dNTP and the templating base; and (iii) burying a protonated base in the hydrophobic environment of the NBP. All of these possibilities would be expected to destabilize the closed ternary complex so that incorporation of incorrect dNTP would be a rare event.
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