title: Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences.
abstract: G-quadruplexes and i-motifs are complementary examples of non-canonical nucleic acid substructure conformations. G-quadruplex thermodynamic stability has been extensively studied for a variety of base sequences, but the degree of duplex destabilization that adjacent quadruplex structure formation can cause has yet to be fully addressed. Stable in vivo formation of these alternative nucleic acid structures is likely to be highly dependent on whether sufficient spacing exists between neighbouring duplex- and quadruplex-/i-motif-forming regions to accommodate quadruplexes or i-motifs without disrupting duplex stability. Prediction of putative G-quadruplex-forming regions is likely to be assisted by further understanding of what distance (number of base pairs) is required for duplexes to remain stable as quadruplexes or i-motifs form. Using oligonucleotide constructs derived from precedented G-quadruplexes and i-motif-forming bcl-2 P1 promoter region, initial biophysical stability studies indicate that the formation of G-quadruplex and i-motif conformations do destabilize proximal duplex regions. The undermining effect that quadruplex formation can have on duplex stability is mitigated with increased distance from the duplex region: a spacing of five base pairs or more is sufficient to maintain duplex stability proximal to predicted quadruplex/i-motif-forming regions.
authors.affiliation: Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK, Institute of Inorganic Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland and University of Nice-Sophia Antipolis, UMR 7272 CNRS, Institut de 40 Chimie de Nice, 28 Avenue Valrose, 06108 Nice, France.
authors.forename: Sebastian L B
authors.initials: SL
authors.lastname: König
authors.forename: Julian L
authors.initials: JL
authors.lastname: Huppert
authors.forename: Roland K O
authors.initials: RK
authors.lastname: Sigel
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Evans
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D002942:Circular Dichroism; D054856:G-Quadruplexes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009691:Nucleic Acid Denaturation; D059372:Nucleotide Motifs; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013696:Temperature; D013816:Thermodynamics
chemical_list: D009841:Oligonucleotides