TDG

TDG belongs to the TDG/mug DNA glycosylase family. Thymine-DNA glycosylase (TDG) removes thymine moieties from G/T mismatches by hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of DNA and the mispaired thymine. With lower activity, this enzyme also removes thymine from C/T and T/T mispairings. TDG can also remove uracil and 5-bromouracil from mispairings with guanine. This enzyme plays a central role in cellular defense against genetic mutation caused by the spontaneous deamination of 5-methylcytosine and cytosine.

Full Name

Thymine DNA Glycosylase

Function

DNA glycosylase that plays a key role in active DNA demethylation: specifically recognizes and binds 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in the context of CpG sites and mediates their excision through base-excision repair (BER) to install an unmethylated cytosine. Cannot remove 5-hydroxymethylcytosine (5hmC). According to an alternative model, involved in DNA demethylation by mediating DNA glycolase activity toward 5-hydroxymethyluracil (5hmU) produced by deamination of 5hmC. Also involved in DNA repair by acting as a thymine-DNA glycosylase that mediates correction of G/T mispairs to G/C pairs: in the DNA of higher eukaryotes, hydrolytic deamination of 5-methylcytosine to thymine leads to the formation of G/T mismatches. Its role in the repair of canonical base damage is however minor compared to its role in DNA demethylation. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and a mispaired thymine. In addition to the G/T, it can remove thymine also from C/T and T/T mispairs in the order G/T>> C/T> T/T. It has no detectable activity on apyrimidinic sites and does not catalyze the removal of thymine from A/T pairs or from single-stranded DNA. It can also remove uracil and 5-bromouracil from mispairs with guanine.

Biological Process

Biological Process base-excision repairIDA:UniProtKB2 Publications
Biological Process base-excision repair, AP site formationIDA:CAFA1 Publication
Biological Process depyrimidinationTAS:Reactome
Biological Process DNA demethylationISS:UniProtKB
Biological Process mismatch repairIDA:UniProtKB1 Publication
Biological Process negative regulation of chromatin bindingIEA:Ensembl
Biological Process negative regulation of protein bindingIEA:Ensembl
Biological Process negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Biological Process oxidative DNA demethylationTAS:Reactome
Biological Process regulation of DNA N-glycosylase activityIMP:CAFA1 Publication
Biological Process regulation of embryonic developmentISS:UniProtKB
Biological Process regulation of gene expression, epigeneticISS:UniProtKB

Cellular Location

Nucleus

PTM

Sumoylation on Lys-330 by either SUMO1 or SUMO2 induces dissociation of the product DNA.