ArticleOncotarget2016
Inhibition of uracil DNA glycosylase sensitizes cancer cells to 5-fluorodeoxyuridine through replication fork collapse-induced DNA damage.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- A multicenter phase II study of TAS-114 in combination with S-1 in patients with pretreated advanced gastric cancer (EPOC1604).Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Trial
- Engineered Allosteric Biosensor for In Situ DNA Glycosylase Detection in Neuroblastoma Risk Stratification and Drug Resistance Monitoring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential.Life science alliance · 2026Article
- Article
- Involvement of the DNA Demethylase Thymine DNA Glycosylase in Anticancer Drug Resistance.Biomolecules & therapeutics · 2025Article
- Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- Ablating UNG activity in a mouse model inhibits colorectal cancer growth by increasing tumor immunogenicity.JCI insight · 2025Article
- Novel telomere-targeting dual-pharmacophore dinucleotide prodrugs for anticancer therapy.Nucleic acids research · 2025Article
- Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA.Scientific reports · 2025Article
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer.Bioscience reports · 2024Review
- Single G-quadruplex-based fluorescence method for the uracil-DNA glycosylase inhibitor screening.Heliyon · 2024Article
- Review
- Metabolomics based plasma biomarkers for diagnosis of oral squamous cell carcinoma and oral erosive lichen planus.Journal of Cancer · 2022Article
- Strengths and Weaknesses of Cell Synchronization Protocols Based on Inhibition of DNA Synthesis.International journal of molecular sciences · 2021Review
- An effective human uracil-DNA glycosylase inhibitor targets the open pre-catalytic active site conformation.Progress in biophysics and molecular biology · 2021Article
- Inhibition of Human Uracil DNA Glycosylase Sensitizes a Large Fraction of Colorectal Cancer Cells to 5-Fluorodeoxyuridine and Raltitrexed but Not Fluorouracil.Molecular pharmacology · 2021Article
- Viruses with U-DNA: New Avenues for Biotechnology.Viruses · 2021Review
- Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA.Frontiers in molecular biosciences · 2021Article
- Non-muscle invasive bladder cancer tissues have increased base excision repair capacity.Scientific reports · 2020Article
- Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.eLife · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
5-fluorodeoxyuridine (5-FdU, floxuridine) is active against multiple cancers through the inhibition of thymidylate synthase, which consequently introduces uracil and 5-FU incorporation into the genome. Uracil DNA glycosylase (UDG) is one of the main enzymes responsible for the removal of uracil and 5-FU. However, how exactly UDG mediates cellular sensitivity to 5-FdU, and if so whether it is through its ability to remove uracil and 5-FU have not been well characterized. In this study, we report that UDG depletion led to incorporation of uracil and 5-FU in DNA following 5-FdU treatment and significantly enhanced 5-FdU's cytotoxicity in cancer cell lines. Co-treatment, but not post-treatment with thymidine prevented cell death of UDG depleted cells by 5-FdU, indicating that the enhanced cytotoxicity is due to the retention of uracil and 5-FU in genomic DNA in the absence of UDG. Furthermore, UDG depleted cells were arrested at late G1 and early S phase by 5-FdU, followed by accumulation of sub-G1 population indicating cell death. Mechanistically, 5-FdU dramatically reduced DNA replication speed in UDG depleted cells. UDG depletion also greatly enhanced DNA damage as shown by γH2AX foci formation. Notably, the increased γH2AX foci formation was not suppressed by caspase inhibitor treatment, suggesting that DNA damage precedes cell death induced by 5-FdU. Together, these data provide novel mechanistic insights into the roles of UDG in DNA replication, damage repair, and cell death in response to 5-FdU and suggest that UDG is a target for improving the anticancer effect of this agent.
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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.