ArticleProceedings of the National Academy of Sciences of the United States of America2005
Probing the active site tightness of DNA polymerase in subangstrom increments.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- Establishing Linkages Among DNA Damage, Mutagenesis, and Genetic Diseases.Chemical research in toxicology · 2022Review
- Determinants of adenine-mutagenesis in diversity-generating retroelements.Nucleic acids research · 2021Article
- Unnatural bases for recognition of noncoding nucleic acid interfaces.Biopolymers · 2021Review
- Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner.Toxics · 2019Review
- Sources of spontaneous mutagenesis in bacteria.Critical reviews in biochemistry and molecular biology · 2018Review
- 1,3-Butadiene-Induced Adenine DNA Adducts Are Genotoxic but Only Weakly Mutagenic When Replicated in Escherichia coli of Various Repair and Replication Backgrounds.Chemical research in toxicology · 2017Article
- NAngewandte Chemie (International ed. in English) · 2017Article
- Variants of sequence family B Thermococcus kodakaraensis DNA polymerase with increased mismatch extension selectivity.PloS one · 2017Article
- Bromopyridone Nucleotide Analogues, Anoxic Selective Radiosensitizing Agents That Are Incorporated in DNA by Polymerases.The Journal of organic chemistry · 2015Article
- Processive Incorporation of Deoxynucleoside Triphosphate Analogs by Single-Molecule DNA Polymerase I (Klenow Fragment) Nanocircuits.Journal of the American Chemical Society · 2015Article
- Emerging critical roles of Fe-S clusters in DNA replication and repair.Biochimica et biophysica acta · 2015Review
- RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications.Critical reviews in biochemistry and molecular biology · 2015Review
- Molecular basis of transcriptional fidelity and DNA lesion-induced transcriptional mutagenesis.DNA repair · 2014Review
- RB69 DNA polymerase structure, kinetics, and fidelity.Biochemistry · 2014Review
- Dissecting the chemical interactions and substrate structural signatures governing RNA polymerase II trigger loop closure by synthetic nucleic acid analogues.Nucleic acids research · 2014Article
- DNA interstrand cross-linking upon irradiation of aryl halide C-nucleotides.The Journal of organic chemistry · 2014Article
- Chemical synthetic biology.Science progress · 2014Review
- Understanding the Molecular Basis of RNA Polymerase II Transcription.Israel journal of chemistry · 2013Article
- DNA mismatch synthesis complexes provide insights into base selectivity of a B family DNA polymerase.Journal of the American Chemical Society · 2013Article
- Expanding the horizon of the thymine isostere biochemistry: unique cyclobutane dimers formed by photoreaction between a thymine and a toluene residue in the dinucleotide framework.Chemistry (Weinheim an der Bergstrasse, Germany) · 2012Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
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Abstract
We describe the use of a series of gradually expanded thymine nucleobase analogs in probing steric effects in DNA polymerase efficiency and fidelity. In these nonpolar compounds, the base size was increased incrementally over a 1.0-A range by use of variably sized atoms (H, F, Cl, Br, and I) to replace the oxygen molecules of thymine. Kinetics studies with DNA Pol I (Klenow fragment, exonuclease-deficient) in vitro showed that replication efficiency opposite adenine increased through the series, reaching a peak at the chlorinated compound. Efficiency then dropped markedly as a steric tightness limit was apparently reached. Importantly, fidelity also followed this trend, with the fidelity maximum at dichlorotoluene, the largest compound that fits without apparent repulsion. The fidelity at this point approached that of wild-type thymine. Surprisingly, the maximum fidelity and efficiency was found at a base pair size significantly larger than the natural size. Parallel bypass and mutagenesis experiments were then carried out in vivo with a bacterial assay for replication. The cellular results were virtually the same as those seen in solution. The results provide direct evidence for the importance of a tight steric fit on DNA replication fidelity. In addition, the results suggest that even high-fidelity replicative enzymes have more steric room than necessary, possibly to allow for an evolutionarily advantageous mutation rate.
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