title: The G-quadruplex ligand telomestatin inhibits POT1 binding to telomeric sequences in vitro and induces GFP-POT1 dissociation from telomeres in human cells.
abstract: Telomestatin is a potent G-quadruplex ligand that specifically interacts with the 3' telomeric overhang, leading to its degradation and that induces a delayed senescence and apoptosis of cancer cells. Protection of Telomere 1 (POT1) was recently identified as a specific single-stranded telomere-binding protein involved in telomere capping and T-loop maintenance. We showed here that a telomestatin treatment inhibits POT1 binding to the telomeric overhang in vitro. The treatment of human EcR293 cells by telomestatin induces a dramatic and rapid delocalization of POT1 from its normal telomere sites but does not affect the telomere localization of the double-stranded telomere-binding protein TRF2. Thus, we propose that G-quadruplex stabilization at telomeric G-overhang inactivates POT1 telomeric function, generating a telomere dysfunction in which chromosome ends are no longer properly protected.
authors.affiliation: Laboratoire d'Onco-Pharmacologie, JE 2428.
authors.forename: Dennis
authors.initials: D
authors.lastname: Gomez
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: O'Donohue
authors.forename: Thomas
authors.initials: T
authors.lastname: Wenner
authors.forename: Céline
authors.initials: C
authors.lastname: Douarre
authors.forename: Jérome
authors.initials: J
authors.lastname: Macadré
authors.forename: Pascale
authors.initials: P
authors.lastname: Koebel
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
authors.forename: Hervé
authors.initials: H
authors.lastname: Kaplan
authors.forename: Alain
authors.initials: A
authors.lastname: Kolkes
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-ya
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Riou
mesh_terms: D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D054856:G-Quadruplexes; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2; D014162:Transfection
chemical_list: D009687:Nuclear Proteins; D010080:Oxazoles; C440849:POT1 protein, human; D011993:Recombinant Fusion Proteins; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins; C504753:TERF2 protein, human; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; C431888:telomestatin; D049452:Green Fluorescent Proteins; D004247:DNA