Divalent transition metal cations counteract potassium-induced quadruplex assembly of oligo(dG) sequences.
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 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-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 I protection assays to demonstrate that competition between quadruplex self-association and triplex assembly is altered in the presence of Mn2+, Co2+or Ni2+. 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.
Blume
S W
SW
Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Guarcello
V
V
Zacharias
W
W
Miller
D M
DM
D002413:Cations, Divalent; D003035:Cobalt / Q000494:pharmacology*; D006801:Humans; D008345:Manganese / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology*; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009838:Oligodeoxyribonucleotides; D011188:Potassium / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism
D002413:Cations, Divalent; D009838:Oligodeoxyribonucleotides; D011687:Purines; D011743:Pyrimidines; C033538:oligodeoxyguanylic acid; D003035:Cobalt; D008345:Manganese; D009532:Nickel; C030986:pyrimidine; D011188:Potassium; C030985:purine