ArticleNucleic acids research2022
Long promoter sequences form higher-order G-quadruplexes: an integrative structural biology study of c-Myc, k-Ras and c-Kit promoter sequences.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Cryo-EM structures of human FANCJ reveal the mechanism of G-quadruplex unwinding and disease-associated mutations.Nature communications · 2026Article
- Oncogene c‑Myc: From molecular mechanism to targeted therapy (Review).Molecular medicine reports · 2026Review
- Article
- Cation-Controlled Assembly, Activity, and Organization of Biomimetic DNA Receptors in Synthetic Cell Membranes.Journal of the American Chemical Society · 2025Article
- Molecular recognition and effects of a benzothiazole derivative targeting the MYC G-quadruplex.Nucleic acids research · 2025Article
- Bridged Azobenzene Exhibits Fully Reversible Photocontrolled Binding to a G‑Quadruplex DNA/Duplex Junction.JACS Au · 2025Article
- MYC in cancer: from undruggable target to clinical trials.Nature reviews. Drug discovery · 2025Review
- PARP2 Catalytic Activity Is Allosterically Stimulated by Binding to the c-KIT1 G-Quadruplex.ACS omega · 2025Article
- Early events in G-quadruplex folding captured by time-resolved small-angle X-ray scattering.Nucleic acids research · 2025Article
- Article
- Early Events in G-quadruplex Folding Captured by Time-Resolved Small-Angle X-Ray Scattering.bioRxiv : the preprint server for biology · 2024Article
- Structural Differences at Quadruplex-Duplex Interfaces Enable Ligand-Induced Topological Transitions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanical Stability and Unfolding Pathways of Parallel Tetrameric G-Quadruplexes Probed by Pulling Simulations.Journal of chemical information and modeling · 2024Article
- Crosstalk between G-Quadruplexes and Dnmt3a-Mediated Methylation of theInternational journal of molecular sciences · 2023Article
- Application of G-quadruplex targets in gastrointestinal cancers: Advancements, challenges and prospects.World journal of gastrointestinal oncology · 2023Review
- Taq-Polymerase Stop Assay to Determine Target Selectivity of G4 Ligands in Native Promoter Sequences ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Structure of a 28.5 kDa duplex-embedded G-quadruplex system resolved to 7.4 Å resolution with cryo-EM.Nucleic acids research · 2023Article
- In Silico Investigation of the Molecular Mechanism of PARP1 Inhibition for the Treatment of BRCA-Deficient Cancers.Molecules (Basel, Switzerland) · 2023Article
- Higher-order G-quadruplexes in promoters are untapped drug targets.Frontiers in chemistry · 2023Review
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8 authors.
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Abstract
We report on higher-order G-quadruplex structures adopted by long promoter sequences obtained by an iterative integrated structural biology approach. Our approach uses quantitative biophysical tools (analytical ultracentrifugation, small-angle X-ray scattering, and circular dichroism spectroscopy) combined with modeling and molecular dynamics simulations, to derive self-consistent structural models. The formal resolution of our approach is 18 angstroms, but in some cases structural features of only a few nucleotides can be discerned. We report here five structures of long (34-70 nt) wild-type sequences selected from three cancer-related promoters: c-Myc, c-Kit and k-Ras. Each sequence studied has a unique structure. Three sequences form structures with two contiguous, stacked, G-quadruplex units. One longer sequence from c-Myc forms a structure with three contiguous stacked quadruplexes. A longer c-Kit sequence forms a quadruplex-hairpin structure. Each structure exhibits interfacial regions between stacked quadruplexes or novel loop geometries that are possible druggable targets. We also report methodological advances in our integrated structural biology approach, which now includes quantitative CD for counting stacked G-tetrads, DNaseI cleavage for hairpin detection and SAXS model refinement. Our results suggest that higher-order quadruplex assemblies may be a common feature within the genome, rather than simple single quadruplex structures.
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