ArticleNucleic acids research2021
Frustrated folding of guanine quadruplexes in telomeric DNA.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Accessibility of telomeric overhangs to stabilizing small-molecule ligands.Nucleic acids research · 2026Article
- Accessibility of Telomeric Overhangs to Stabilizing Small-Molecule Ligands.bioRxiv : the preprint server for biology · 2025Article
- Auto-luminescence study of thermal unfolding of DNA G-quadruplexes.RSC advances · 2025Article
- The Zuo1 C-terminal domain stabilizes DNA guanosine quadruplex (G4) structures located on Chromosome IX in Saccharomyces cerevisiae.Nucleic acids research · 2025Article
- Computer Folding of Parallel DNA G-Quadruplex: Hitchhiker's Guide to the Conformational Space.Journal of computational chemistry · 2025Article
- Protection of the Telomeric Junction by the Shelterin Complex.Journal of the American Chemical Society · 2024Article
- Protection of the Telomeric Junction by the Shelterin Complex.bioRxiv : the preprint server for biology · 2024Article
- Exploring the Landscape of Aptamers: From Cross-Reactive to Selective to Specific, High-Affinity Receptors for Cocaine.JACS Au · 2024Article
- Structure, Topology, and Stability of Multiple G-quadruplexes in Long Telomeric Overhangs.Journal of molecular biology · 2024Review
- Structural effects of inosine substitution in telomeric DNA quadruplex.Frontiers in chemistry · 2024Article
- Inhibited complete folding of consecutive human telomeric G-quadruplexes.Nucleic acids research · 2023Article
- Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters.International journal of molecular sciences · 2022Article
- Shelterin reduces the accessibility of telomeric overhangs.Nucleic acids research · 2022Article
- Emerging accessibility patterns in long telomeric overhangs.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Thermally Induced Transitions of d(GLife (Basel, Switzerland) · 2022Article
- Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications.Pharmaceuticals (Basel, Switzerland) · 2022Article
- G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin.Frontiers in chemistry · 2022Article
- Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human chromosomes terminate in long, single-stranded, DNA overhangs of the repetitive sequence (TTAGGG)n. Sets of four adjacent TTAGGG repeats can fold into guanine quadruplexes (GQ), four-stranded structures that are implicated in telomere maintenance and cell immortalization and are targets in cancer therapy. Isolated GQs have been studied in detail, however much less is known about folding in long repeat sequences. Such chains adopt an enormous number of configurations containing various arrangements of GQs and unfolded gaps, leading to a highly frustrated energy landscape. To better understand this phenomenon, we used mutagenesis, thermal melting, and global analysis to determine stability, kinetic, and cooperativity parameters for GQ folding within chains containing 8-12 TTAGGG repeats. We then used these parameters to simulate the folding of 32-repeat chains, more representative of intact telomeres. We found that a combination of folding frustration and negative cooperativity between adjacent GQs increases TTAGGG unfolding by up to 40-fold, providing an abundance of unfolded gaps that are potential binding sites for telomeric proteins. This effect was most pronounced at the chain termini, which could promote telomere extension by telomerase. We conclude that folding frustration is an important and largely overlooked factor controlling the structure of telomeric DNA.
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