ArticleChemical research in toxicology2012
In-vitro replication studies on O(2)-methylthymidine and O(4)-methylthymidine.
Article in Chemical research in toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed, 17 citations in OpenAlex.
- DNA Replication across α-l-(3'-2')-Threofuranosyl Nucleotides Mediated by Human DNA Polymerase η.Biochemistry · 2024Article
- Article
- Metabolic Activation and DNA Interactions of CarcinogenicInternational journal of molecular sciences · 2022Review
- Collision-Induced Dissociation Studies of Protonated Ions of Alkylated Thymidine and 2'-Deoxyguanosine.Journal of the American Society for Mass Spectrometry · 2020Article
- Mammalian DNA Polymerase Kappa Activity and Specificity.Molecules (Basel, Switzerland) · 2019Review
- DNA Polymerase ν Rapidly Bypasses OChemical research in toxicology · 2016Article
- Replicative Bypass of OChemical research in toxicology · 2016Article
- Lesion Orientation ofChemical science · 2016Article
- In Vitro Lesion Bypass Studies of O(4)-Alkylthymidines with Human DNA Polymerase η.Chemical research in toxicology · 2016Article
- DNA Polymerases η and ζ Combine to Bypass O(2)-[4-(3-Pyridyl)-4-oxobutyl]thymine, a DNA Adduct Formed from Tobacco Carcinogens.Chemical research in toxicology · 2016Article
- Mass Spectrometry-Based Quantitative Strategies for Assessing the Biological Consequences and Repair of DNA Adducts.Accounts of chemical research · 2016Review
- Mass spectrometry for the assessment of the occurrence and biological consequences of DNA adducts.Chemical Society reviews · 2015Review
- Roles of translesion synthesis DNA polymerases in the potent mutagenicity of tobacco-specific nitrosamine-derived O2-alkylthymidines in human cells.DNA repair · 2015Article
- Syntheses and characterizations of the in vivo replicative bypass and mutagenic properties of the minor-groove O2-alkylthymidine lesions.Nucleic acids research · 2014Article
- Replication across regioisomeric ethylated thymidine lesions by purified DNA polymerases.Chemical research in toxicology · 2013Article
- Translesion synthesis of 8,5'-cyclopurine-2'-deoxynucleosides by DNA polymerases η, ι, and ζ.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
O(2)- and O(4)-methylthymidine (O(2)-MdT and O(4)-MdT) can be induced in tissues of laboratory animals exposed with N-methyl-N-nitrosourea, a known carcinogen. These two O-methylated DNA adducts have been shown to be poorly repaired and may contribute to the mutations arising from exposure to DNA methylating agents. Here, in vitro replication studies with duplex DNA substrates containing site-specifically incorporated O(2)-MdT and O(4)-MdT showed that both lesions blocked DNA synthesis mediated by three different DNA polymerases, including the exonuclease-free Klenow fragment of Escherichia coli DNA polymerase I (Kf(-)), human DNA polymerase κ (pol κ), and Saccharomyces cerevisiae DNA polymerase η (pol η). Results from steady-state kinetic measurements and LC-MS/MS analysis of primer extension products revealed that Kf(-) and pol η preferentially incorporated the correct nucleotide (dAMP) opposite O(2)-MdT, while O(4)-MdT primarily directed dGMP misincorporation. While steady-state kinetic experiments showed that pol κ-mediated nucleotide insertion opposite O(2)-MdT and O(4)-MdT is highly promiscuous, LC-MS/MS analysis of primer extension products demonstrated that pol κ favorably incorporated the incorrect dGMP opposite both lesions. Our results underscored the limitation of the steady-state kinetic assay in determining how DNA lesions compromise DNA replication in vitro. In addition, the results from our study revealed that, if left unrepaired, O-methylated thymidine lesions may constitute important sources of nucleobase substitutions emanating from exposure to alkylating agents.
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Registered trials
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.