TDGmediated

TDGmediated refers to cellular processes driven by thymine-DNA glycosylase (TDG), particularly its role in base excision repair and active DNA demethylation. TDG is a DNA repair enzyme that recognizes and excises damaged or inappropriate bases, and it also participates in epigenetic regulation by processing oxidized forms of cytosine.

The central mechanism of TDG-mediated demethylation involves the action of TET enzymes, which oxidize 5-methylcytosine to 5-hydroxymethylcytosine and further to 5-formylcytosine and 5-carboxylcytosine. TDG recognizes and excises these oxidized cytosine derivatives, creating abasic sites. The base excision repair machinery, including AP endonuclease and DNA polymerase, fills the gap with unmodified cytosine, resulting in a net loss of the methyl group from the original cytosine. In this way, TDG mediates an active pathway for DNA demethylation that can influence gene expression and chromatin state. TDG also retains its canonical glycosylase activity for removing thymine from G:T mismatches, contributing to genomic stability.

Biological significance of TDG-mediated pathways includes regulation of gene expression during development and cellular differentiation, as well as responses to environmental cues that alter epigenetic marks. Dysregulation of TDG activity or its interactions with other base excision repair factors can disrupt methylation patterns and has been linked to various diseases, including cancer and neurodevelopmental disorders. Regulation of TDG activity occurs through protein interactions and post-translational modifications that modulate its catalytic efficiency and chromatin access.