Telomeric G-overhang DNA structure (G-overhang) (G-overhang)

The telomeric G-overhang DNA structure is a single-stranded, guanine-rich sequence at the 3' terminus of eukaryotic chromosomes, typically ranging from 50 to 400 nucleotides in length (PMID: 11532439). Its primary biological role is to facilitate the formation of the T-loop, a protective structure that sequesters the chromosome end to prevent it from being recognized as a double-strand break by the DNA damage response machinery (PMID: 10360576). In the majority of human cancers, the enzyme telomerase is upregulated and utilizes this G-overhang as a substrate to append hexameric repeats, thereby maintaining telomere length and enabling replicative immortality (PMID: 23396253). Therapeutic intervention focuses on small molecules, such as G-quadruplex (G4) stabilizers, which induce the G-overhang to fold into stable four-stranded structures (PMID: 21572414). This folding sterically hinders telomerase access and displaces telomere-protective proteins, leading to "telomere uncapping," the induction of DNA damage foci, and subsequent apoptosis or senescence in malignant cells (PMID: 28163010).

Other names

Telomeric 3' overhangG-rich overhangTelomeric G-tailSingle-stranded telomeric DNA

Stabilization of G-quadruplex (G4) structures within the single-stranded overhang to inhibit telomerase-mediated extension and induce telomere uncapping and DNA damage responses.