G-quadruplexes, bioinformatics

Quadruplexes are noncanonical DNA structures that arise in guanine rich loci and have important bio-logical functions. Classically, quadruplexes contain four stacked intramolecular G-tetrads. Surprisingly,although some algorithms allow searching for longer than 4G tracts for quadruplex formation, these havenot yet been systematically studied. Therefore, we analyzed the human genome for sequences that arepredicted to adopt stacked intramolecular G-tetrads with greater than four stacks. The data provideevidence for numerous G-quadruplexes that contain five or six stacked intramolecular G-tetrads. Thesesequences are predominantly found in known gene regulatory regions. Electrophoretic mobility assaysand circular dichroism spectroscopy indicate that these sequences form quadruplex structures in vitrounder physiological conditions. The localization and in vitro stability of these G-quadruplexes indicatetheir potentially important roles in gene regulation and their potential for therapeutic applications.