Comparative Effects of Mercury(II) and Cadmium on MutS Homolog 6(MSH6)‐Mediated DNA Mismatch Binding Activities in Zebrafish ( Danio rerio ) Embryos

MutS homolog 6 (MSH6) of the MSH2–MSH6 complex binds simple mispairs and small insertion‐deletion loops (IDL) then initiates DNA mismatch repair in eukaryotes. We have shown the ability of Cd 2+ to downregulate msh2/msh6 expression in zebrafish embryos via oxidative stress. This study explored the effects of Cd 2+ and Hg 2+ on MSH6‐mediated mismatch binding activities. MSH6‐mediated G‐T and IDL‐specific binding activities were significantly inhibited at similar levels after exposing zebrafish embryos at 1 h postfertilization) to HgCl 2 or CdCl 2 at 1.0 to 2.5 μM for 9 h, but MSH6 synthesis was found to be less sensitive to Hg 2+ than to Cd 2+ . Real‐time RT‐PCR and in situ hybridization also detected a weaker susceptibility of MSH gene transcription to Hg 2+ . The weaker response of MSH gene activities to Hg 2+ correlated with the lower oxidative stress‐inducing potential of Hg 2+ . Hence, Hg 2+ targets mismatch sensing capacity at protein function rather than at transcription level .