ArticleNucleic acids research2012
Force spectroscopy reveals the DNA structural dynamics that govern the slow binding of Actinomycin D.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 75 citations in OpenAlex.
- From single DNA molecule to nanoparticle formation: mechanistic basis for monocationic aromatic drug-induced DNA frameworks.Journal of nanobiotechnology · 2026Article
- Binuclear ruthenium complex linker length tunes DNA threading intercalation kinetics.Biophysical journal · 2025Article
- TMPyP binding evokes a complex, tunable nanomechanical response in DNA.Nucleic acids research · 2024Article
- Discovery of a new highly pathogenic toxin involved in insect sepsis.Microbiology spectrum · 2023Article
- Ouabain-Induced Changes in the Expression of Voltage-Gated Potassium Channels in Epithelial Cells Depend on Cell-Cell Contacts.International journal of molecular sciences · 2022Article
- Actinomycin D: a novel Pseudomonas aeruginosa quorum sensing inhibitor from the endophyte Streptomyces cyaneochromogenes RC1.World journal of microbiology & biotechnology · 2022Article
- Prostaglandin E2 Enhances Gap Junctional Intercellular Communication in Clonal Epithelial Cells.International journal of molecular sciences · 2021Article
- Article
- Truncated TALE-FP as DNA Staining Dye in a High-salt Buffer.Scientific reports · 2019Article
- Anticooperative Binding Governs the Mechanics of Ethidium-Complexed DNA.Biophysical journal · 2019Article
- Single-molecule polarization microscopy of DNA intercalators sheds light on the structure of S-DNA.Science advances · 2019Article
- Recent Developments in the Interactions of Classic Intercalated Ruthenium Compounds: [Ru(bpy)₂dppz]Molecules (Basel, Switzerland) · 2019Review
- ZYH005, a novel DNA intercalator, overcomes all-trans retinoic acid resistance in acute promyelocytic leukemia.Nucleic acids research · 2018Article
- Article
- Freezing shortens the lifetime of DNA molecules under tension.Journal of biological physics · 2017Article
- Single molecule high-throughput footprinting of small and large DNA ligands.Nature communications · 2017Article
- DNA intercalation optimized by two-step molecular lock mechanism.Scientific reports · 2016Article
- Mechanisms of small molecule-DNA interactions probed by single-molecule force spectroscopy.Nucleic acids research · 2016Article
- Involvement of phosphorylated Apis mellifera CREB in gating a honeybee's behavioral response to an external stimulus.Learning & memory (Cold Spring Harbor, N.Y.) · 2016Article
- Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation.Biophysical journal · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Actinomycin D (ActD) is a small molecule with strong antibiotic and anticancer activity. However, its biologically relevant DNA-binding mechanism has never been resolved, with some studies suggesting that the primary binding mode is intercalation, and others suggesting that single-stranded DNA binding is most important. To resolve this controversy, we develop a method to quantify ActD's equilibrium and kinetic DNA-binding properties as a function of stretching force applied to a single DNA molecule. We find that destabilization of double stranded DNA (dsDNA) by force exponentially facilitates the extremely slow ActD-dsDNA on and off rates, with a much stronger effect on association, resulting in overall enhancement of equilibrium ActD binding. While we find the preferred ActD-DNA-binding mode to be to two DNA strands, major duplex deformations appear to be a pre-requisite for ActD binding. These results provide quantitative support for a model in which the biologically active mode of ActD binding is to pre-melted dsDNA, as found in transcription bubbles. DNA in transcriptionally hyperactive cancer cells will therefore likely efficiently and rapidly bind low ActD concentrations (≈ 10 nM), essentially locking ActD within dsDNA due to its slow dissociation, blocking RNA synthesis and leading to cell death.
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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.