TATA-BINDING PROTEIN DISCRIMINATES BETWEEN DIFFERENT LESIONS ON DNA, RESULTING IN A TRANSCRIPTION DECREASE

DNA damage recognition by basal transcription factors follows differen t mechanisms. Using transcription-competition, nitrocellulose filter b inding, and DNase I footprinting assays, we show that, although the ge neral transcription factor TFIIH is able to target any kind of lesion which can be repaired by the nucleotide excision repair pathway, TATA binding protein (TBP)-TFIID is more selective in damage recognition. O nly genotoxic agents which are able to induce kinked DNA structures si milar to the one for the TATA box in its TBP complex are recognized. I ndeed, DNase I footprinting patterns reveal that TBP protects equally 4 nucleotides upstream and 6 nucleotides downstream from the A-T (at p osition -29 of the noncoding strand) of the adenovirus major late prom oter and from the G-G of a cisplatin-induced 1,2-d(GpG) cross-link. To gether, our results may partially explain differences in transcription inhibition rates following DNA damage.