Pol κ SNP variants, like WT, show an increase in melting temperature in the presence of preferred DNA substrates and the correct nucleotide. (A) Melting temperatures of pol κ variants in the presence of undamaged DNA, N2ffdG, and incoming nucleotides dC (correct nucleotide) or dT (incorrect nucleotide). Stabilization of the variants is observed in the presence of both undamaged and N2ffdG DNA templates with the correct nucleotide present but not with the incorrect nucleotide or with DNA alone. (B) The same increase is not seen with the major groove adducts, N6ffdA and ethenodA. There is no increase in melting temperature in the presence of either major groove adduct or in the presence of the correct nucleotide (dT for the major groove adducts) and DNA.