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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Saintomé C,Amrane S,Mergny JL,Alberti P

doi

10.1093/nar/gkw003

subject

Has Abstract

pub_date

2016-04-07 00:00:00

pages

2926-35

issue

6

eissn

0305-1048

issn

1362-4962

pii

gkw003

journal_volume

44

pub_type

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