TDG Protein, Human (His)

TDG is a DNA glycosylase that plays a key role in active DNA demethylation by specifically recognizing and binding 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) at CpG sites, mediating their excision through base-excision repair (BER) to install an unmethylated cytosine. It cannot remove 5-hydroxymethylcytosine (5hmC). Alternatively, it may participate in DNA demethylation by acting on 5-hydroxymethyluracil (5hmU) produced from 5hmC deamination. It also functions in DNA repair as a thymine-DNA glycosylase, correcting G/T mispairs to G/C pairs—hydrolytic deamination of 5-methylcytosine to thymine in higher eukaryotes leads to G/T mismatches. Its role in repairing canonical base damage is minor compared to DNA demethylation. TDG hydrolyzes the carbon-nitrogen bond between the DNA sugar-phosphate backbone and mispaired thymine. Beyond G/T, it excises thymine from C/T and T/T mispairs with activity order G/T >> C/T > T/T. It shows no activity on apyrimidinic sites and does not remove thymine from A/T pairs or single-stranded DNA. Additionally, it can excise uracil and 5-bromouracil from mispairs with guanine.