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.