Interaction of telomestatin with the telomeric single-strand overhang

摘要: The extremities of chromosomes end in a G-rich single-stranded overhang that has been implicated the onset replicative senescence. repeated sequence forming G-overhang is able to adopt peculiar four-stranded DNA structure vitro called G-quadruplex, which poor substrate for telomerase. Small molecule ligands selectively stabilize telomeric G-quadruplex induce telomere shortening and delayed growth arrest. Here we show ligand telomestatin dramatic effect on conformation intracellular G-overhangs. Competition experiments indicate strongly binds vivo impairs its conformation. Long-term treatment cells with greatly reduces size, as evidenced by specific hybridization or oligonucleotide ligation assay experiments, concomitant loss cell viability. In protection using dimethyl sulfate also alters G-overhangs, result compatible formation local quadruplex at overhang. Altogether these support hypothesis an target action telomestatin.