Bulletin du Cancer


G-quadruplex DNA: myth or reality? Volume 90, issue 4, Avril 2003


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Institut fédératif de recherche 53, UFR de Pharmacie, Université de Reims-Champagne-Ardenne, 51, rue Cognacq-Jay, 51096 Reims. CNRS UMR 6142, Université de Reims-Champagne-Ardenne, 51096 Reims

The peculiar sequence of telomeric DNA, composed of repetitions of the GGTTAG motif allows the formation of an unusual DNA conformation based on guanine-quadruplex (G-quadruplex). Small molecules that bind and stabilize telomeric DNA under its G-quadruplex conformation are able to impair telomerase activity. Several recent reports have shown that G-quadruplex ligands could block telomerase activity in cancer cells and represent a new experimental approach to limit cancer growth. The intracellular existence of G-quadruplex structure is still controversial, since no direct proof allowed to establish its reality. Many sequences of nucleic acids in the mammalian genome are able to form a G-quadruplex in vitro and several proteins have been described to interact in vitro with G-quadruplex. These data indicated that G-quadruplex are members of a family of target structures larger than that initially described at telomeres, and raised the question of the selectivity and therapeutic index of their ligands in the context of an antitumor therapy.