Structural polymorphism of homopurine-homopyrimidine sequences at neutral pH

Under superhelical strain and mildly acidic pH, polyd(GA).polyd(CT) sequences are known to adopt an H-y3 conformer of H-DNA. We studied the effects of the sequence length, metal ions, and pH on the structures formed by polyd(GA).polyd(CT) sequences in supercoiled plasmid DNA at bacterial superhelicity. The results from experiments that distinguish multiple structures forming in a given plasmid DNA population strongly suggest that polyd(GA).polyd(CT) sequences of 33 base-pairs or more can adopt both H-y3 and H-y5 isomeric forms of H-DNA at neutral pH either with or without magnesium ions. At pH 5 in the presence of zinc ions, H-DNA is formed. However, at pH 7 in the presence of zinc ions, polyd(GA).polyd(CT) sequences form an intramolecular d(GA).d(GA).d(CT) triplex similar to a dG.dG.dC triplex, which is stabilized with magnesium ions for poly(dG).poly(dC) sequences. Zinc ions also stabilize the dG.dG.dC triplex for relatively long poly(dG).poly(dC) sequences (more than 24 base-pairs at pH 7).