THERMODYNAMIC AND BASE-PAIRING STUDIES OF MATCHED AND MISMATCHED DNA DODECAMER DUPLEXES CONTAINING CIS-SYN, (6-4)-PHOTOPRODUCTS AND DEWAR PHOTOPRODUCTS OF TT

Cis-syn dimers, (6-4) products and their Dewar valence isomers are the major photoproducts of DNA and have different mutagenic properties an d rates of repair. To begin to understand the physical basis for these differences, the thermal stability and base pairing properties of the corresponding photoproducts of the TT site in d(GAGTATTATGAG) were in vestigated, The (6-4) and Dewar products destabilize the duplex form b y similar to 6 kcal/mol of free energy at 37 degrees C relative to the parent, whereas a cis-syn dimer only destabilizes the duplex form by 1.5 kcal/mol, Duplexes with G opposite the 3'-T of the (6-4) and Dewar products are more stable than those with A by similar to 0.4 kcal/mol , whereas the cis-syn dimer prefers A over G by 0.7 kcal/mol, Proton N MR suggests that wobble base pairing takes place between the 3'-T of t he cis-syn dimer and an opposed G, whereas there is no evidence of sig nificant H-bonding between these two bases in the (6-4) product, The t hermodynamic and H-bonding data for the (6-4) product are consistent w ith a 4 nt interior loop structure which may facilitate flipping of th e photoproduct in and out of the helix.