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 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 gammaH2AX foci colocalized at telomeres.
Rodriguez
Raphaël
R
The University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK.
Müller
Sebastian
S
Yeoman
Justin A
JA
Trentesaux
Chantal
C
Riou
Jean-François
JF
Balasubramanian
Shankar
S
D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics*; D006801:Humans; D015394:Molecular Structure; D000089804:Shelterin Complex; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*
C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins