Divalent transition metal cations counteract potassium-induced quadruplex assembly of oligo(dG) sequences

Abstract

Nucleic acids containing tracts of contiguous guanines tend to self-associate into four-stranded (quadruplex) structures, based on reciprocal non-Watson-Crick (G(*)G(*)G(*)G) hydrogen bonds. The quadruplex structure is induced/stabilized by monovalent cations, particularly potassium. Using circular dichroism, we have determined that the induction/stabilization of quadruplex structure by K + is specifically counteracted by low concentrations of Mn 2+ (4-10 mM), Co 2+ (0.3-2 mM) or Ni 2+ (0.3-0.8 mM). G-Tract-containing single strands are also capable of sequence-specific non-Watson-Crick interaction with d(G·C)-tract-containing (target) sequences within double-stranded DNA. The assembly of these G(*)G·C-based triple helical structures is supported by magnesium, but is potently inhibited by potassium due to sequestration of the G-tract single strand into quadruplex structure. We have used DNase protection assays to demonstrate that competition between quadruplex self-association and triplex assembly is altered in the presence of Mn 2+, Co 2+ Or Ni 2+. By specifically counteracting the induction/stabilization of quadruplex structure by potassium, these divalent transition metal cations allow triplex formation in the presence of K + and shift the position of equilibrium so that a very high proportion of triplex target sites are bound. Thus, variation of the cation environment can differentially promote the assembly of multistranded nucleic acid structural alternatives.