G-Quadruplex stabilization by telomestatin induces TRF2 protein dissociation from telomeres and anaphase bridge formation accompanied by loss of the 3′ telomeric overhang in cancer cells

摘要: Inhibition of telomerase activity by inhibitors induces a gradual loss telomeres, and this in turn causes cancer cells to enter crisis stage. Here, we report the inhibitor telomestatin, which is known stabilize G-quadruplex structures at 3' single-stranded telomeric overhangs (G-tails), rapidly dissociates TRF2 from telomeres within week, when given concentration that does not cause normal die. The G-tails were dramatically reduced upon short-term treatment with drug cell lines, but fibroblasts epithelial cells. In addition, telomestatin also induced anaphase bridge formation lines. These effects similar those dominant negative TRF2, prompt an bridge. results indicate exerts its anticancer effect only through inhibiting telomere elongation, disrupting capping function very ends telomeres. Unlike conventional require long-term treatments, stabilizer death, it was selectively effective This study identifies protein as therapeutic target for treating many types have caps DNA each chromosome.