Human telomeric G-quadruplex DNA (hTel G4)

Human telomeric G-quadruplex DNA is a non-canonical secondary structure formed by the guanine-rich tandem repeats (TTAGGG) at the ends of human chromosomes [6, 7]. These structures are composed of stacked G-tetrads stabilized by Hoogsteen hydrogen bonds and monovalent cations, typically potassium or sodium [1, 6]. In most cancer cells, telomere length is maintained by the overexpressed enzyme telomerase, which prevents the natural senescence that occurs in somatic cells [3, 12]. Small molecule ligands designed to target and stabilize these G-quadruplexes can physically block telomerase access and displace protective shelterin proteins like POT1 [2, 13]. This uncapping of the telomere is recognized by the cell as a double-strand break, triggering a robust DNA damage response that leads to apoptosis or permanent growth arrest [2, 10]. As such, the human telomeric G-quadruplex represents a promising therapeutic target for broad-spectrum anticancer drug development [4, 8].

Other names

Telomeric G-quadruplexhTel G4Human telomeric G4Telomeric DNA G-quadruplexhTel-G4G4-DNA

Stabilization of the G-quadruplex structure at the 3' telomeric overhang, which inhibits telomerase-mediated telomere extension and displaces telomere-binding proteins such as POT1, leading to telomere uncapping, activation of the DNA damage response, and subsequent induction of apoptosis or senescence [2, 6, 10].