Chemical Biology Tools to unravel biological functions of nucleic acids secondary structures
DNA and RNA containing runs of 3 or 4 adjacent guanines may spontaneously arrange into four-stranded DNA supramolecular structures called G-quadruplexes (G4). These non-canonical structures are likely to form in G-rich regions throughout the genome and thus are assumed to have functional roles in key biological processes, such as replication, transcription, repair, and recombination, and thereby they represent potential barriers for the enzymatic machineries involved in these processes. However, the dynamic nature of these structures makes their identification in live cells extremely challenging; therefore, G4 actual formation in vivo is still a matter of debate. G4 can be stabilized by small synthetic molecules (G4 ligands), hence, the latter represent a new family of DNA / RNA drugs assumed to act region selectively at specific genomic G-rich loci. In general, G4 ligands do not display acute cytotoxicity and produce diverse cellular effects, suggesting that targeting of genomic G4 is characterized by different accessibility. Consequently, it is highly important to follow G4 ligand distribution in cells and identify precisely their binding sites genome- and transcriptome-wide; this knowledge will enhance understanding in regard to characterization and exploitation of drug responses.
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Dr, Chercheur UMR 9187/U 1196, Institut Curie, Orsay, FR
Chimie et Modélisation pour la Biologie du Cancer (UMR9187 / U1196)