Stereochemistry and Position-Dependent Effects of Carcinogens on TATA/TBP Binding

ABSTRACT

The TATA-box binding protein (TBP) is required by eukaryotic RNA polymerases to bind to the TATA box, an eight-basepair DNA promoter element, to initiate transcription. Carcinogen adducts that bind to the TATA box can hamper this important process. Benzo[a]pyrene (BP) is a representative chemical carcinogen that can be metabolically converted to highly reactive benzo[a]pyrene diol epoxides (BPDE), which in turn can form chemically stereoisomeric BP-DNA adducts. Depending on the TATA-bound adduct's location and stereochemistry, TATA/TBP binding can be decreased or increased. Our previous study interpreted the location-dependent effect in terms of conformational freedom and …