Role of Alkali Metal Ions in G-Quadruplex Nucleic Acid Structure and Stability

Abstract

G-quadruplexes are guanine-rich nucleic acids that fold by forming successive quartets of guanines (the G-tetrads), stabilized by intra-quartet hydrogen bonds, inter-quartet stacking, and cation coordination. This specific although highly polymorphic type of secondary structure deviates significantly from the classical B-DNA duplex. G-quadruplexes are detectable in human cells and are strongly suspected to be involved in a number of biological processes at the DNA and RNA levels. The vast structural polymorphism exhibited by G-quadruplexes, together with their putative biological relevance, makes them attractive therapeutic targets compared to canonical duplex DNA. This chapter focuses on the essential and specific coordination of alkali metal cations by G-quadruplex nucleic acids, and most notably on studies highlighting cation-dependent dissimilarities in their stability, structure, formation, and interconversion. Section 1 surveys G-quadruplex structures and their interactions with alkali metal ions while Section 2 presents analytical methods used to study G-quadruplexes. The influence of alkali cations on the stability, structure, and kinetics of formation of G-quadruplex structures of quadruplexes will be discussed in Sections 3 and 4. Section 5 focuses on the cation-induced interconversion of G-quadruplex structures. In Sections 3 to 5, we will particularly emphasize the comparisons between cations, most often K(+) and Na(+) because of their prevalence in the literature and in cells.

Unraveling the Thermodynamics of the Folding and Interconversion of Human Telomere G‐Quadruplexes

“…The contributions describing A→H transition (Fig. 2b) show that H conformation is more populated than A mainly due to favorable ion (de)hydration effect (Na + hydration, K + dehydration; Δ G ion ≪ 0) which is in agreement with the generally accepted interpretation of Na + and K + influence on the quadruplex stability [9] . H conformation is slightly favored over A also by other hydration contributions (Δ G hyd < 0) and higher conformational freedom (Δ G conf < 0).…”

Folding and misfolding pathways of G-quadruplex DNA

“…Structures with at least two stacked G-quartets are called G-quadruplexes. G-quadruplex stabilization is ensured by monovalent cations such as Na + , K + or NH 4 + (14,15), which they intercalate between consecutive G-quartets and are octa-coordinated by the O6 of the guanines (16). G-quadruplexes can adopt different topologies (Figure 1) (17), and this structural polymorphism is exploited in applications such as DNA functionalization and nanodevices (18–20).…”

G Quadruplex in Plants: A Ubiquitous Regulatory Element and Its Biological Relevance

“…Adding to the complexity of the G4 DNA structure, the stacks of G-quartets are connected by loops of variable sizes (1–7 nucleotides) and orientations (parallel or antiparallel) (Wang and Patel, 1993; Parkinson et al, 2002; Huppert, 2010). These secondary structures are stabilized by cations, preferably potassium ion (K + ) (Largy et al, 2016). G quadruplex structures form in RNA as well as DNA and may be intermolecular or intramolecular depending on number of nucleic acid strands involved in the quadruplex formation.…”