DIVALENT TRANSITION-METAL CATIONS COUNTERACT POTASSIUM-INDUCED QUADRUPLEX ASSEMBLY OF OLIGO(DG) SEQUENCES

Nucleic acids containing tracts of contiguous guanines tend to self-as sociate into four-stranded (quadruplex) structures, based on reciproca l non-Watson-Crick (GG*G*G) hydrogen bonds. The quadruplex structure is induced/stabilized by monovalent cations, particularly potassium. U sing circular dichroism, we have determined that the induction/stabili zation of quadruplex structure by K+ is specifically counteracted by l ow concentrations of Mn2+ (4-10 mM), Co2+ (0.3-2 mM) or Ni2+ (0.3-0.8 mM). G-Tract-containing single strands are also capable of sequence-sp ecific non-Watson-Crick interaction with d(G . C)-tract-containing (ta rget) sequences within double-stranded DNA. The assembly of these GG . C-based triple helical structures is supported by magnesium, but is potently inhibited by potassium due to sequestration of the G-tract si ngle strand into quadruplex structure. We have used DNase I protection assays to demonstrate that competition between quadruplex self-associ ation and tripler assembly is altered in the presence of Mn2+, Co2+ or Ni2+. By specifically counteracting the induction/stabilization of qu adruplex structure by potassium, these divalent transition metal catio ns allow tripler formation in the presence of K+ and shift the positio n of equilibrium so that a very high proportion of tripler target site s are bound. Thus, variation of the cation environment can differentia lly promote the assembly of multistranded nucleic acid structural alte rnatives.