Recognition of a cytosine base lesion by a human damage-specific DNA binding protein.
Sodium bisulfite reacts with cytosine and 5-methylcytosine, forming the 5,6-dihydrosulfonate adducts which deaminate to the uracil and thymine adducts, respectively. At alkaline pH, the sulfonate groups are then released, generating uracil and thymine. In DNA, the resulting G:U and G:T base mismatches generated are potential sites of mutagenesis. Using a human damage-specific DNA binding protein as a probe, we have found protein-recognizable lesions in bisulfite-treated DNA and poly d(I-C), but not in treated poly d(A-T) or poly d(A-U). Although this suggests that the lesion recognized is cytosine-derived, there was no correlation between the number of uracils induced and the number of binding sites, suggesting that the protein-bound damage is not a uracil-containing mismatch. Modification of the treatment protocol to reduce elimination of the bisulfite from the base adducts increased the level of binding, suggesting that the protein recognizes a base-sulfonate adduct.
D003596:Cytosine / Q000378:metabolism*; D045647:DNA Glycosylases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D013447:Sulfites / Q000378:metabolism; D013696:Temperature; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase
D004268:DNA-Binding Proteins; D013447:Sulfites; D014498:Uracil; D003596:Cytosine; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; C042345:hydrogen sulfite