Model Studies On Mechanism Of DNA Photoreactivation

DNA is damaged by ultraviolet component from sunlight to give a variety of potentially mutagenic photoproducts. The two major lessons formed in DNA by this radiation are the cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproduct, which constitute 70-80% and 20-30% of the total photoproducts, respectively. These lesions will block replication and transcription of DNA, leading to cytotoxic and mutagenic effects. The two photolessions can be repaired through DNA photoreactivation catalyzed by CPD photolyase and (6-4) photolyase, respectively.Several model compounds that mimic the action of photolyase have been designed, such as a chromophore attached to a pyrimidine dimer. Studies performed with these compounds have been helpful to unravel the mechanisms of the DNA photolyases in detail. However, these are still many unsolved questions on the physical-chemical mechanisms involved in the whole process. In particular, it is unclear what factors make the enzyme mediate a very high efficiency (Φ = 0.7-0.98) for DNA photoreactivation including the energy and electron transfer. In addition, under excitation with 280 nm light, Trp277, as a substrate at binding site, can also directly repair CPD with a relatively high quantum yield (Φ = 0.56) via an electron transfer reaction.Model systems exhibited two reverse solvent-dependence with efficient splitting in various polarity solvents, such as Φ = 0.06-0.40 for indole-dimer systems, and 0.062-0.016 for flavin-dimer systems, in various polar solvents from water to 1,4-dioxance. An explanation for this observation comes from the reasoning that model systems would not stabilize the charge-separated species, in which the electron is at the acceptor dimer before cleavage. Hence, an unproductive back electron transfer competed with the cleavage of dimer radical anion is an important factor to lead to the low efficiency.Therefore, we investigated the photoreaction of the model of the CPDs and mechanisms of the photophysical-chemical proceeds.