Zn ions improve the fidelity of metal-mediated primer extension while suppressing intrinsic and Mn-induced mutagenic effects by DNA polymerases.

While Mn ions are well-established for reducing the fidelity of DNA polymerases, leading to the misincorporation of nucleotides, our investigation of the effects of metal ions revealed a contrasting role of Zn. Here, we demonstrate that Zn ions enhance the fidelity of DNA polymerases (the 3' → 5' exonuclease-deficient Klenow fragment and Taq DNA polymerase) by suppressing misincorporation during primer extension reactions. Remarkably, Zn ions inhibit both intrinsic misincorporation and Mn-induced misincorporation of nucleotides.