title: Quadruplex-forming properties of FRAXA (CGG) repeats interrupted by (AGG) triplets.
abstract: The (CGG) repeats associated with X-chromosome fragility are generally believed to form quadruplexes. This notion has persisted although it had been shown that only very short (CGG)(n) sequences form quadruplexes and that this quadruplex formation occurs in conditions far from physiological. We have now studied, using CD and absorption spectroscopies, quadruplex formation of (CGG)(n) (n=4, 7, 8, or 16) and their analogs interrupted by (AGG) triplets under various solvent conditions. In healthy individuals, (AGG) triplets are interspersed throughout the (CGG) repeat regions and appear to hinder (CGG)(n) motif expansion. Here we show that (CGG) repeats do not form quadruplexes under physiological conditions in aqueous solution but, interestingly, quadruplexes are readily formed in water-ethanol solutions. The presence of (AGG) triplets markedly stabilized quadruplex formation. Quadruplexes may thus hinder rather than support (CGG)(n) motif expansion.
authors.affiliation: Laboratory of CD Spectroscopy of Nucleic Acids, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, CZ-61265 Brno, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Renciuk
authors.forename: Michal
authors.initials: M
authors.lastname: Zemánek
authors.forename: Iva
authors.initials: I
authors.lastname: Kejnovská
authors.forename: Michaela
authors.initials: M
authors.lastname: Vorlícková
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D006860:Hydrogen Bonding; D008297:Male; D009690:Nucleic Acid Conformation; D018911:Trinucleotide Repeats; D014867:Water / Q000737:chemistry
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D014867:Water