title: The exception that confirms the rule: a higher-order telomeric G-quadruplex structure more stable in sodium than in potassium.
abstract: DNA and RNA guanine-quadruplexes (G4s) are stabilized by several cations, in particular by potassium and sodium ions. Generally, potassium stabilizes guanine-quartet assemblies to a larger extent than sodium; in this article we report about a higher-order G4 structure more stable in sodium than in potassium. Repeats of the DNA GGGTTA telomeric motif fold into contiguous G4 units. Using three independent approaches (thermal denaturation experiments, isothermal molecular-beacon and protein-binding assays), we show that the (GGGTTA)7GGG sequence, folding into two contiguous G4 units, exhibits an unusual feature among G4 motifs: despite a lower thermal stability, its sodium conformation is more stable than its potassium counterpart at physiological temperature. Using differential scanning calorimetry and mutated sequences, we show that this switch in the relative stability of the sodium and potassium conformations (occurring around 45 °C in 100 mM cation concentration) is the result of a more favorable enthalpy change upon folding in sodium, generated by stabilizing interactions between the two G4 units in the sodium conformation. Our work demonstrates that interactions between G4 structural domains can make a higher-order structure more stable in sodium than in potassium, even though its G4 structural domains are individually more stable in potassium than in sodium.
authors.affiliation: Structure et Instabilité des Génomes, Sorbonne Universités, Muséum national d'Histoire naturelle, Inserm U 1154, CNRS UMR 7196, Paris, France UPMC (Université Pierre et Marie Curie) Université Paris 6, UFR 927, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Saintomé
authors.affiliation: Université de Bordeaux, ARNA Laboratory, Bordeaux, France IECB (Institut Européen de Chimie et Biologie), Inserm U 869, Pessac, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Amrane
authors.affiliation: Université de Bordeaux, ARNA Laboratory, Bordeaux, France IECB (Institut Européen de Chimie et Biologie), Inserm U 869, Pessac, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
authors.affiliation: Structure et Instabilité des Génomes, Sorbonne Universités, Muséum national d'Histoire naturelle, Inserm U 1154, CNRS UMR 7196, Paris, France alberti@mnhn.fr.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Alberti
mesh_terms: D002414:Cations, Monovalent; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D015335:Molecular Probes; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D009841:Oligonucleotides / Q000737:chemistry; D011188:Potassium / Q000737:chemistry*; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D020871:RNA Stability; D051716:Replication Protein A / Q000737:chemistry; D012964:Sodium / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D002414:Cations, Monovalent; D015335:Molecular Probes; D009841:Oligonucleotides; D051716:Replication Protein A; D012313:RNA; D004247:DNA; D012964:Sodium; D011188:Potassium