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 Tm while other metals caused small to moderate changes in Tm at 11 or 110 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.