ArticleNucleic acids research2014
Structural basis for inhibition of DNA replication by aphidicolin.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 143 citations in OpenAlex.
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- Hypoxia-induced genome-wide DNA demethylation by DNMT3A and EMT of cancer cells.Cellular & molecular biology letters · 2025Article
- Synthetic Studies toward the Aphidicolin Family of Diterpenoid Natural Products.The Journal of organic chemistry · 2025Article
- Structure and biochemistry-guided engineering of an all-RNA system for DNA insertion with R2 retrotransposons.Nature communications · 2025Article
- Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy.Discover oncology · 2025Review
- Replicative DNA polymerase epsilon and delta holoenzymes show wide-ranging inhibition at G-quadruplexes in the human genome.Nucleic acids research · 2025Article
- Mcm5 mutation leads to silencing of Stat1-bcl2 which accelerating apoptosis of immature T lymphocytes with DNA damage.Cell death & disease · 2025Article
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- The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs.Molecular cancer therapeutics · 2024Article
- Genome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC).bioRxiv : the preprint server for biology · 2024Article
- Evidence of interactions among apoptosis, cell proliferation, and dedifferentiation in the rudiment during whole-organ intestinal regeneration in the sea cucumber.Developmental biology · 2024Article
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- Molecular choreography of primer synthesis by the eukaryotic Pol α-primase.Nature communications · 2023Article
- Molecular choreography of primer synthesis by the eukaryotic Pol α-primase.bioRxiv : the preprint server for biology · 2023Article
- Structures of human primosome elongation complexes.Nature structural & molecular biology · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Natural tetracyclic diterpenoid aphidicolin is a potent and specific inhibitor of B-family DNA polymerases, haltering replication and possessing a strong antimitotic activity in human cancer cell lines. Clinical trials revealed limitations of aphidicolin as an antitumor drug because of its low solubility and fast clearance from human plasma. The absence of structural information hampered the improvement of aphidicolin-like inhibitors: more than 50 modifications have been generated so far, but all have lost the inhibitory and antitumor properties. Here we report the crystal structure of the catalytic core of human DNA polymerase α (Pol α) in the ternary complex with an RNA-primed DNA template and aphidicolin. The inhibitor blocks binding of dCTP by docking at the Pol α active site and by rotating the template guanine. The structure provides a plausible mechanism for the selectivity of aphidicolin incorporation opposite template guanine and explains why previous modifications of aphidicolin failed to improve its affinity for Pol α. With new structural information, aphidicolin becomes an attractive lead compound for the design of novel derivatives with enhanced inhibitory properties for B-family DNA polymerases.
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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.