ArticleNucleic acids research2024
Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 8 citations in OpenAlex.
- Targeting RPRD1B overcomes chemoresistance in gastric cancer by suppressing the TOPBP1-mediated DNA damage repair pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- In situ sol-gel-sol transformation formed by sodium alginate realizes folic acid-modified chitosan nanoparticles to deliver hops β-acids for colorectal cancer therapy.Journal of nanobiotechnology · 2026Article
- Epigenetic Biomarkers for Predicting Nucleoside Analog Drug Response and Resistance in Cancer.Biomolecules · 2026Review
- Ferroptosis as a Novel Therapeutic Strategy to Overcome Multidrug Resistance in Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Reactive Oxygen Species: Molecular Mechanisms, Cellular Targets, and Implications for Genomic Stability.BioMed research international · 2026Review
- Deciphering the Role of DNA Polymerase Eta on the Incorporation and Bypass of Inosine and Cell Cycle Arrest.International journal of molecular sciences · 2025Article
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- Review
- Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer.Frontiers in chemistry · 2025Article
- Review
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer.Bioscience reports · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent in colorectal cancer, and resistance to 5-FU easily emerges. One of the mechanisms of drug action and resistance of 5-FU is through DNA incorporation. Our quantitative reverse-transcription PCR data showed that one of the translesion synthesis (TLS) DNA polymerases, DNA polymerase η (polη), was upregulated within 72 h upon 5-FU administration at 1 and 10 μM, indicating that polη is one of the first responding polymerases, and the only TLS polymerase, upon the 5-FU treatment to incorporate 5-FU into DNA. Our kinetic studies revealed that 5-fluoro-2'-deoxyuridine triphosphate (5FdUTP) was incorporated across dA 41 and 28 times more efficiently than across dG and across inosine, respectively, by polη indicating that the mutagenicity of 5-FU incorporation is higher in the presence of inosine and that DNA lesions could lead to more mutagenic incorporation of 5-FU. Our polη crystal structures complexed with DNA and 5FdUTP revealed that dA:5FdUTP base pair is like dA:dTTP in the active site of polη, while 5FdUTP adopted 4-enol tautomer in the base pairs with dG and HX increasing the insertion efficiency compared to dG:dTTP for the incorrect insertions. These studies confirm that polη engages in the DNA incorporation and bypass of 5-FU.
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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.