Random Formation of G-Quadruplexes in the Full-Length Human Telomere Overhangs Leads to a Kinetic Folding Pattern with Targetable Vacant G-Tracts
Year: 2018
Type: article
Abstract: G-Quadruplexes formed in the 3' telomere overhang (∼200 nucleotides) have been shown to regulate biological functions of human telomeres. The mechanism governing the population pattern of multiple telomeric G-quadruplexes is yet to be elucidated inside the telomeric overhang in a time window shorter than thermodynamic equilibrium. Using a single-molecule force ramping assay, we quantified G-quadruplex populations in telomere overhangs over a full physiological range of 99-291 nucleotides. We found that G-quadruplexes randomly form in these overhangs within seconds, which leads to a population governed by a kinetic, rather than a thermodynamic, folding pattern. The kinetic folding gives rise to vacant G-tracts between G-quadruplexes. By targeting these vacant G-tracts using complementary DNA fragments, we demonstrated that binding to the telomeric G-quadruplexes becomes more efficient and specific for telomestatin derivatives.
Source: Biochemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Development of high throughput screening method of G-quadruplexes using small molecules, Selective detection and stabilization of G-quadruplexes in genome using G4 ligands, G5244472638, DNA三次元構造の動的変化を可視化する蛍光性低分子リガンドの創成, Development of Light-up type G-quadruplex ligand for live cell imaging, G7388638063, 機能性グアニン四重鎖を選択的に安定化するリガンドの創製研究, G8552958798, G868833290, G974567579
OpenAlex ID: W2902448518