ArticleJournal of the American Chemical Society2019
Defining the Role of Nucleotide Flipping in Enzyme Specificity Using
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Robust excision of different purine lesions by homologs thymine DNA glycosylase and mismatch-specific uracil DNA-glycosylase.The Journal of biological chemistry · 2026Article
- Mapping DNA glycosylase binding across lesion sequence contexts reveals extended sequence and structural recognition logic.Nature communications · 2026Article
- Thymine DNA glycosylase binds to R-loops and excises 5-formyl and 5-carboxyl cytosine from DNA/RNA hybrids.The Journal of biological chemistry · 2026Article
- Observing nucleotide flipping in DNA using indirect 2'-F nucleotide probes and 19F NMR.Nucleic acids research · 2025Article
- Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.Nature communications · 2025Article
- Thymine DNA glycosylase combines sliding, hopping, and nucleosome interactions to efficiently search for 5-formylcytosine.Nature communications · 2024Article
- Mechanism of Dual-Site Recognition in a Classic DNA Aptamer.Journal of chemical information and modeling · 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
- Backbone Conformational Equilibrium in Mismatched DNA Correlates with Enzyme Activity.Biochemistry · 2023Article
- 4'-SCFAngewandte Chemie (International ed. in English) · 2022Article
- Measuring thermodynamic preferences to form non-native conformations in nucleic acids using ultraviolet melting.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Kinetic Analysis of the Effect ofBiochemistry · 2022Article
- Kinetics and thermodynamics of BI-BII interconversion altered by T:G mismatches in DNA.Biophysical journal · 2022Article
- Energy Landscapes for Base-Flipping in a Model DNA Duplex.The journal of physical chemistry. B · 2022Article
- Developments in solution-state NMR yield broader and deeper views of the dynamic ensembles of nucleic acids.Current opinion in structural biology · 2021Review
- Structural Insights into the Mechanism of Base Excision by MBD4.Journal of molecular biology · 2021Article
- TET-TDG Active DNA Demethylation at CpG and Non-CpG Sites.Journal of molecular biology · 2021Article
- Atomic resolution of short-range sliding dynamics of thymine DNA glycosylase along DNA minor-groove for lesion recognition.Nucleic acids research · 2021Article
- Inequality in the Frequency of the Open States Occurrence Depends on SingleMolecules (Basel, Switzerland) · 2020Article
- 2'-Fluorinated Hydantoins as Chemical Biology Tools for Base Excision Repair Glycosylases.ACS chemical biology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A broad range of proteins employ nucleotide flipping to recognize specific sites in nucleic acids, including DNA glycosylases, which remove modified nucleobases to initiate base excision repair. Deamination, a pervasive mode of damage, typically generates lesions that are recognized by glycosylases as being foreign to DNA. However, deamination of 5-methylcytosine (mC) generates thymine, a canonical DNA base, presenting a challenge for damage recognition. Nevertheless, repair of mC deamination is important because the resulting G·T mispairs cause C → T transition mutations, and mC is abundant in all three domains of life. Countering this threat are three types of glycosylases that excise thymine from G·T mispairs, including thymine DNA glycosylase (TDG). These enzymes must minimize excision of thymine that is not generated by mC deamination, in A·T pairs and in polymerase-generated G·T mispairs. TDG preferentially removes thymine from DNA contexts in which cytosine methylation is prevalent, including CG and one non-CG site. This remarkable context specificity could be attained through modulation of nucleotide flipping, a reversible step that precedes base excision. We tested this idea using fluorine NMR and DNA containing 2'-fluoro-substituted nucleotides. We find that dT nucleotide flipping depends on DNA context and is efficient only in contexts known to feature cytosine methylation. We also show that a conserved Ala residue limits thymine excision by hindering nucleotide flipping. A linear free energy correlation reveals that TDG attains context specificity for thymine excision through modulation of nucleotide flipping. Our results provide a framework for characterizing nucleotide flipping in nucleic acids using
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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.