Preferential binding of a G-quadruplex ligand to human chromosome ends
| العنوان: | Preferential binding of a G-quadruplex ligand to human chromosome ends |
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| المؤلفون: | Lydia Riou, Patrick Mailliet, Jean-François Riou, Laurent Gauthier, Anne De Cian, Bernard Dutrillaux, Christine Granotier, François D. Boussin, Eliane Mandine, Françoise Hoffschir, Jean-Louis Mergny, Gaëlle Pennarun, Dennis Gomez |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Telomerase, Guanine, Pyridines, Biology, G-quadruplex, Ligands, Article, chemistry.chemical_compound, Cell Line, Tumor, Genetics, Chromosomes, Human, Humans, heterocyclic compounds, Lymphocytes, Binding site, Metaphase, Cells, Cultured, Binding Sites, Ligand, DNA, Telomere, Molecular biology, G-Quadruplexes, chemistry, Cell culture, Quinolines |
| الوصف: | The G-overhangs of telomeres are thought to adopt particular conformations, such as T-loops or G-quadruplexes. It has been suggested that G-quadruplex structures could be stabilized by specific ligands in a new approach to cancer treatment consisting in inhibition of telomerase, an enzyme involved in telomere maintenance and cell immortality. Although the formation of G-quadruplexes was demonstrated in vitro many years ago, it has not been definitively demonstrated in living human cells. We therefore investigated the chromosomal binding of a tritiated G-quadruplex ligand, 3H-360A (2,6-N,N′-methyl-quinolinio-3-yl)-pyridine dicarboxamide [methyl-3H]. We verified the in vitro selectivity of 3H-360A for G-quadruplex structures by equilibrium dialysis. We then showed by binding experiments with human genomic DNA that 3H-360A has a very potent selectivity toward G-quadruplex structures of the telomeric 3′-overhang. Finally, we performed autoradiography of metaphase spreads from cells cultured with 3H-360A. We found that 3H-360A was preferentially bound to chromosome terminal regions of both human normal (peripheral blood lymphocytes) and tumor cells (T98G and CEM1301). In conclusion, our results provide evidence that a specific G-quadruplex ligand interacts with the terminal ends of human chromosomes. They support the hypothesis that G-quadruplex ligands induce and/or stabilize G-quadruplex structures at telomeres of human cells. |
| اللغة: | English |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d947eb34158506b72834c5eb3086f41f http://europepmc.org/articles/PMC1181860 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d947eb34158506b72834c5eb3086f41f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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