Description
Background: In the DNA of higher eukaryotes, hydrolytic deamination of 5-methylcytosine to thymine leads to the formation of G/T mismatches. G/T mismatch-specific Thymine DNA Glycosylase (TDG) is a nuclear protein which corrects G/T mismatches to G/C pairs by hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and the mispaired thymine. TDG also corrects a subset of G/U mispairs inefficiently removed by the more abundant uracil glycosylases. Retinoic acid receptors interact physically and functionally with TDG, enhancing the ability of the retinoid X receptor and the retinoid X receptor/retinoid acid receptor complex to bind to their response elements. TDG interacts with, and is covalently modified by, the ubiquitin-like proteins SUMO-1 and SUMO-2/3, resulting in a reduction of the DNA substrate and AP site binding affinity of TDG. This sumoylation is associated with a significant increase in enzymatic turnover in reactions with a G/U substrate and the loss of G/T processing activity