Model Studies of DNA Photorepair: Reduction Potentials of Thymine and Cytosine Cyclobutane Dimers Measured by Fluorescence Quenching

The interactions of various pyrimidines (1,3-dimethylthymine, DMT, 1,3-bis(N4,N4-dimethylcytosin-1yl)propane, DMC) and their corresponding cis-syn cyclobutane dimers (DMTD and DMCD) with a series of excitedstate electron donors were examined with the goal of understanding the energetics and mechanism of UV repair by DNA photolyase. For each substrate there is a good correlation between the excited state oxidation potential (Eox*) and the quenching rate constant (kq). The value for kq increases as Eox* becomes more negative, asymptotically approaching a value that is at or below the solvent diffusion limit. These data all showed good fits to the RehmWeller equation. Reduction potentials for each of the substrates could be extracted from this analysis: -2.20 V (vs SCE) for DMTD; -2.14 V for DMT; -2.17 V for DMCD; and -2.16 for DMC. These values show that the initial electron transfer step in the photolyase mechanism is exergonic by ca. 10-15 kcal/mol. Thus these data support the reductive electron transfer mechanism for DNA photolyases proposed by Jorns et al. (J. Biol. Chem. 1987, 262, 486-491).