ArticleChemical research in toxicology2012
Presteady state kinetic investigation of the incorporation of anti-hepatitis B nucleotide analogues catalyzed by noncanonical human DNA polymerases.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Conformational gating governs nucleotide incorporation by a DNA-crosslinked polymerase.Nucleic acids research · 2026Article
- Extrahepatic malignancies and antiviral drugs for chronic hepatitis B: A nationwide cohort study.Clinical and molecular hepatology · 2024Article
- [Impact of nucleosides analogues and nucleotide analogues on the outcomes related to chronic hepatitis B based on non-antiviral effects].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Review
- Hepatitis B Virus Treatment and Hepatocellular Carcinoma: Controversies and Approaches to Consensus.Liver cancer · 2022Review
- Interlocking activities of DNA polymerase β in the base excision repair pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Compatibility and Fidelity of Mirror-Image Thymidine in Transcription Events by T7 RNA Polymerase.Molecular therapy. Nucleic acids · 2020Article
- Risk of Hepatocellular Carcinoma in Patients Treated With Entecavir vs Tenofovir for Chronic Hepatitis B: A Korean Nationwide Cohort Study.JAMA oncology · 2019Observational
- Elucidating molecular interactions ofCommunications biology · 2019Article
- Structural basis for the D-stereoselectivity of human DNA polymerase β.Nucleic acids research · 2017Article
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol.DNA repair · 2017Article
- Genetic Evidence for Genotoxic Effect of Entecavir, an Anti-Hepatitis B Virus Nucleotide Analog.PloS one · 2016Article
- Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase.Nucleic acids research · 2014Article
- Structural basis for the binding and incorporation of nucleotide analogs with L-stereochemistry by human DNA polymerase λ.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Recent insight into the kinetic mechanisms and conformational dynamics of Y-Family DNA polymerases.Biochemistry · 2014Review
- HeberNasvac: Development and Application in the Context of Chronic Hepatitis B.Euroasian journal of hepato-gastroenterologyReview
- The antiretroviral 2',3'-dideoxycytidine causes mitochondrial dysfunction in proliferating and differentiated HepaRG human cell cultures.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Antiviral nucleoside analogues have been developed to inhibit the enzymatic activities of the hepatitis B virus (HBV) polymerase, thereby preventing the replication and production of HBV. However, the usage of these analogues can be limited by drug toxicity because the 5'-triphosphates of these nucleoside analogues (nucleotide analogues) are potential substrates for human DNA polymerases to incorporate into host DNA. Although they are poor substrates for human replicative DNA polymerases, it remains to be established whether these nucleotide analogues are substrates for the recently discovered human X- and Y-family DNA polymerases. Using presteady state kinetic techniques, we have measured the substrate specificity values for human DNA polymerases β, λ, η, ι, κ, and Rev1 incorporating the active forms of the following anti-HBV nucleoside analogues approved for clinical use: adefovir, tenofovir, lamivudine, telbivudine, and entecavir. Compared to the incorporation of a natural nucleotide, most of the nucleotide analogues were incorporated less efficiently (2 to >122,000) by the six human DNA polymerases. In addition, the potential for entecavir and telbivudine, two drugs which possess a 3'-hydroxyl, to become embedded into human DNA was examined by primer extension and DNA ligation assays. These results suggested that telbivudine functions as a chain terminator, while entecavir was efficiently extended by the six enzymes and was a substrate for human DNA ligase I. Our findings suggested that incorporation of anti-HBV nucleotide analogues catalyzed by human X- and Y-family polymerases may contribute to clinical toxicity.
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