RETINOIC ACID RECEPTORS INTERACT PHYSICALLY AND FUNCTIONALLY WITH THET-G MISMATCH-SPECIFIC THYMINE-DNA GLYCOSYLASE

The pleiotropic effects of retinoids are mediated by nuclear receptors that are activated by 9-cis- or all-trans-retinoic acid to function a s ligand-dependent transcription factors. In a yeast one-hybrid screen for proteins capable of interacting with native retinoic acid recepto r (RAR), we have isolated the T:G mismatch-specific thymine-DNA glycos ylase (TDG), which initiates the repair of T:G mismatches caused by sp ontaneous deamination of methylated cytosines. Here, we report that TD G can interact with RAR and the retinoid X receptor (RXR) in a ligand- independent manner, both in yeast and in vitro. Mapping of the binding sites revealed interaction with a region of the ligand binding domain harboring alpha-helix 1 in both RAR and RXR. In transient transfectio n experiments, TDG potentiated transactivation by RXR from a direct re peat element spaced by one nucleotide (DR1) and by RXR/RAR heterodimer s from a direct repeat element spaced by five nucleotides (DR5). In vi tro, TDG enhanced RXR and RXR/RAR binding to their response elements. These data indicate that TDG is not only a repair enzyme, but could al so function in the control of transcription.