Effects of methylation on a synthetic polynucleotide: the B--Z transition in poly(dG-m5dC).poly(dG-m5dC).

TLDR

High‑salt solutions induce a B‑to‑Z transition in poly(dG‑dC).poly(dG‑dC) with characteristic spectral changes, and the methylated poly(dG‑m5dC).poly(dG‑m5dC) shows a similar transition at much lower, physiologically relevant salt concentrations. The study compared solution behavior of the methylated synthetic polynucleotide poly(dG‑m5dC).poly(dG‑m5dC) with that of the unmethylated poly(dG‑dC).poly(dG‑dC). The methylated polymer undergoes a B‑to‑Z transition at Mg²⁺ concentrations three orders of magnitude lower than the unmethylated polymer, and mixed copolymers containing m5dC‑dG exhibit an even greater propensity for the transition.

Abstract

We have compared the behavior in solution of the synthetic polynucleotide poly(dG-m5dC).poly(dG-m5dC) with that of the unmethylated polynucleotide poly(dG-dC).poly(dG-dC). In solutions containing high concentrations of salt, poly(dG-dC).poly(dG-dC) is known to exhibit altered circular dichroic and absorption spectra correlated with formation of a left-handed Z DNA structure. Poly(dG-m5dC).poly(dG-m5dC) behaves similarly, but the spectral transition from the B to the Z form occurs at much lower salt concentrations, close to usual physiological conditions. Divalent and polyvalent ions are particularly effective: The B--Z transition of poly(dG-m5dC).(dG-m5dC) can be induced at a Mg2+ concentration three orders of magnitude lower than that required for the unmethylated polymer. We have also studied mixed copolymers containing both dC and m5dC. Our results suggest that the sequence m5dC-dG, which occurs in eukaryotic DNA, can have a disproportionately large effect on the B--Z transition.