ArticleNucleic acids research2020
The hTERT core promoter forms three parallel G-quadruplexes.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Structure-Informed Design of Distinct Parallel G-Quadruplex Stabilizers for KRAS-Driven Cancer Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- Dual targeting of topoisomerase I and DNA G-quadruplexes enhances senescence and chemosensitivity in colorectal cancer.Communications biology · 2026Article
- The immortality mechanism of TERT promoter mutant cancers is self-reinforcing and reversible.Molecular cell · 2025Article
- Modulation of dynamic DNA G-quadruplex structures in the hTERT promoter region by ligands.Nucleic acids research · 2024Article
- Potential protein kinase inhibitors that target G-quadruplex DNA structures in the human telomeric regions.Molecular diversity · 2024Article
- Article
- Co-delivery of artemisinin and metformin via PEGylated niosomal nanoparticles: potential anti-cancer effect in treatment of lung cancer cells.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- Telomeres and telomerase in Sarcoma disease and therapy.International journal of medical sciences · 2024Review
- Structure, Topology, and Stability of Multiple G-quadruplexes in Long Telomeric Overhangs.Journal of molecular biology · 2024Review
- Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States.Genes · 2023Article
- Application of G-quadruplex targets in gastrointestinal cancers: Advancements, challenges and prospects.World journal of gastrointestinal oncology · 2023Review
- Probing juxtaposed G-quadruplex and hairpin motifs using a responsive nucleoside probe: a unique scaffold for chemotherapy.Chemical science · 2023Article
- Stable bulged G-quadruplexes in the human genome: identification, experimental validation and functionalization.Nucleic acids research · 2023Article
- Taq-Polymerase Stop Assay to Determine Target Selectivity of G4 Ligands in Native Promoter Sequences ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Structure of a 28.5 kDa duplex-embedded G-quadruplex system resolved to 7.4 Å resolution with cryo-EM.Nucleic acids research · 2023Article
- Inhibited complete folding of consecutive human telomeric G-quadruplexes.Nucleic acids research · 2023Article
- Higher-order G-quadruplexes in promoters are untapped drug targets.Frontiers in chemistry · 2023Review
- "Dynamical Docking" of Cyclic Dinuclear Au(I) Bis-N-heterocyclic Complexes Facilitates Their Binding to G-Quadruplexes.Inorganic chemistry · 2022Article
- Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters.International journal of molecular sciences · 2022Article
- Hormonal regulation of telomerase activity and hTERT expression in steroid-regulated tissues and cancer.Cancer cell international · 2022Review
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8 authors.
Funding
Abstract
The structure of the 68 nt sequence with G-quadruplex forming potential within the hTERT promoter is disputed. One model features a structure with three stacked parallel G-quadruplex units, while another features an unusual duplex hairpin structure adjoined to two stacked parallel and antiparallel quadruplexes. We report here the results of an integrated structural biology study designed to distinguish between these possibilities. As part of our study, we designed a sequence with an optimized hairpin structure and show that its biophysical and biochemical properties are inconsistent with the structure formed by the hTERT wild-type sequence. By using circular dichroism, thermal denaturation, nuclear magnetic resonance spectroscopy, analytical ultracentrifugation, small-angle X-ray scattering, molecular dynamics simulations and a DNase I cleavage assay we found that the wild type hTERT core promoter folds into a stacked, three-parallel G-quadruplex structure. The hairpin structure is inconsistent with all of our experimental data obtained with the wild-type sequence. All-atom models for both structures were constructed using molecular dynamics simulations. These models accurately predicted the experimental hydrodynamic properties measured for each structure. We found with certainty that the wild-type hTERT promoter sequence does not form a hairpin structure in solution, but rather folds into a compact stacked three-G-quadruplex conformation.
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