Thymine-DNA glycosylase (TDG)

Thymine-DNA glycosylase (TDG) is an enzyme primarily responsible for "removing thymine bases from G·T mismatches" in double-stranded DNA, a process that arises when 5-methylcytosine undergoes deamination to thymine[2][3]. TDG catalyzes the hydrolysis of the N-glycosidic bond between thymine and deoxyribose, generating an abasic site that is further processed by the base excision repair (BER) pathway[2][3][4]. Beyond this canonical repair function, TDG is pivotal in "active DNA demethylation", excising oxidized derivatives of 5-methylcytosine (such as 5-formylcytosine and 5-carboxylcytosine), thereby playing an important role in epigenetic regulation and gene expression[1][2][4]. TDG interacts with multiple nuclear receptors (including estrogen receptor, glucocorticoid receptor, androgen receptor, vitamin D receptor) and transcription factors, modulating gene regulatory networks and chromatin architecture[2][4]. Loss or dysfunction of TDG is associated with increased genomic instability and cancer susceptibility, highlighting its dual roles in maintaining genome integrity and regulating the epigenome[4]. No clinically established small-molecule inhibitors or drugs are known to target TDG directly as of current knowledge.

Other names

G/T mismatch-specific thymine DNA glycosylasehTDGThymine DNA glycosylase

For hypothetical or research-targeted drugs: enzyme inhibition or modulation; potential interference with base excision repair or demethylation pathways