Thymidine DNA glycosidase (TDG) belongs to the superfamily of monofunctional uracil DNA glycosidase, which plays a dual role in genome stability and epigenetic regulation. TDG participates in the regulation of DNA methylation and demethylation. DNA methylation is mainly cytosine (C) methylation, which refers to the formation of 5-methylcytosine (5mC) by adding a methyl to the 5th carbon atom of cytosine under the action of DNA methyltransferase (DNMTs) with S-adenosylmethionine (SAM) as methyl donor. And 5mC is widely distributed in mammalian genomes and plays an important role in maintaining genomic stability, tissue-specific gene silencing, and reverse transcription transposon silencing and many other biological processes. DNA demethylation refers to the reduction of 5mC to C, which is also accomplished by DNMTs. DNA demethylation includes two ways: passive demethylation and active demethylation. Passive DNA demethylation refers to the passive dilution of newly synthesized sub-stranded DNA that fails to maintain its methylation state during DNA replication; Active demethylation of DNA does not involve DNA replication. It refers to the removal of 5-methyl-cytosine (5mC) and 5-carboxy-cytosine (5hmC) oxides, i.e.5-methyl-hydroxy-cytosine (5fC) and 5-carboxy-cytosine (5caC), by enzymes such as TDG. TDG also cleaves N-glycoside bonds between sugars and target bases through the base excision repair pathway (BER) and plays an important role in correcting mismatched and damaged DNA base pairs (bps). Recent studies have shown that TDG also plays an important role in transcriptional regulation, embryonic development and tumor therapy. This paper summarizes the research status and progress of TDG in recent years, and provides theoretical support for further in-depth study.
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