Heavy metal ions interactions with G-quadruplex-prone DNA sequences

Abstract

The industrial world exposes living organisms to a variety of metal pollutants. Here we investigated whether such elements affect G-rich sequences susceptible to fold into G-quadruplex (GQ) structures. Thermal stability and conformation of these oligoncleotides was studied at various molar ratios of a variety of heavy metal salts using thermal FRET, transition-FRET (t-FRET) and circular dichroism. Metal ions affected the thermal stability of the GQs to different extents; some metals had no effect on T_m while other metals caused small to moderate changes in T_m at 1:1 or 1:10 molar ratio. While most of the metals had no major effect, Al³⁺, Cd²⁺, Pb²⁺, Hg²⁺ and Zn²⁺ altered the thermal stability and structural features of the GQs. Some metals such as Pb²⁺ and Hg²⁺ exhibit differential interactions with telomere, c-myc and c-kit GQs. Overall, toxic heavy metals affect G-quadruplex stability in a sequence and topology dependent manner. This study provides new insight into how heavy metal exposure may affect gene expression and cellular responses.

Keywords: Al(3+); Cd(2+); G-quadruplex (GQ); Heavy metal; Hg(2+); Pb(2+); Telomere; Zn(2+); c-kit; c-myc.