A Novel Small Molecule That Alters Shelterin Integrity and Triggers a DNA-Damage Response at Telomeres

We describe a novel synthetic small molecule which shows an unprecedented stabilization of the human telomeric G-quadruplex with high selectivity relative to double-stranded DNA. We report that this compound can be used in vitro to inhibit telomerase activity and to uncap human POT1 (protection of t...

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Veröffentlicht in:Journal of the American Chemical Society 2008-11, Vol.130 (47), p.15758-15759
Hauptverfasser: Rodriguez, Raphaël, Müller, Sebastian, Yeoman, Justin A, Trentesaux, Chantal, Riou, Jean-François, Balasubramanian, Shankar
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Sprache:eng
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Zusammenfassung:We describe a novel synthetic small molecule which shows an unprecedented stabilization of the human telomeric G-quadruplex with high selectivity relative to double-stranded DNA. We report that this compound can be used in vitro to inhibit telomerase activity and to uncap human POT1 (protection of telomeres 1) from the telomeric G-overhang. We also show that the small molecule G-quadruplex binder induces a partial alteration of shelterin through POT1 uncapping from telomeres in human HT1080 cancer cells and the presence of γH2AX foci colocalized at telomeres.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja805615w