ArticleProceedings of the National Academy of Sciences of the United States of America2011
Replication infidelity via a mismatch with Watson-Crick geometry.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
- Extended sequence context shapes mutational bias inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Nature communications · 2026Article
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Research square · 2025Article
- Probing rare and short-lived conformational states in nucleic acids using off-resonance carbonyl and guanidino carbon RJournal of magnetic resonance (San Diego, Calif. : 1997) · 2025Article
- Structure of a DNA Glycosylase Bound to a Nicked T:G Mismatch-Containing DNA.Molecules (Basel, Switzerland) · 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
- Electronic and Nuclear Quantum Effects on Proton Transfer Reactions of Guanine-Thymine (G-T) Mispairs Using Combined Quantum Mechanical/Molecular Mechanical and Machine Learning Potentials.Molecules (Basel, Switzerland) · 2024Article
- Quantitative and systematic NMR measurements of sequence-dependent A-T Hoogsteen dynamics uncovers unique conformational specificity in the DNA double helix.bioRxiv : the preprint server for biology · 2024Article
- Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer.Nucleic acids research · 2024Article
- Melanoma-Derived DNA Polymerase Theta Variants Exhibit Altered DNA Polymerase Activity.Biochemistry · 2024Article
- DNA polymerase λ Loop1 variant yields unexpected gain-of-function capabilities in nonhomologous end-joining.DNA repair · 2024Article
- NMR measurements of transient low-populated tautomeric and anionic Watson-Crick-like G·T/U in RNA:DNA hybrids: implications for the fidelity of transcription and CRISPR/Cas9 gene editing.Nucleic acids research · 2024Article
- A unified Watson-Crick geometry drives transcription of six-letter expanded DNA alphabets by E. coli RNA polymerase.Nature communications · 2023Article
- Dynamic basis for dA•dGTP and dA•d8OGTP misincorporation via Hoogsteen base pairs.Nature chemical biology · 2023Article
- Polγ coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.Nature structural & molecular biology · 2023Article
- Structural insights into viral genome replication by the severe fever with thrombocytopenia syndrome virus L protein.Nucleic acids research · 2023Article
- Quantum Tunnelling Effects in the Guanine-Thymine Wobble Misincorporation via Tautomerism.The journal of physical chemistry letters · 2023Article
- Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair.Nature communications · 2022Article
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
In describing the DNA double helix, Watson and Crick suggested that "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson-Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base-base mismatch with Watson-Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson-Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson-Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G • T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA.
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