SELECTIVE DNA THYMINE DIMERIZATION DURING UVA IRRADIATION IN THE PRESENCE OF A SATURATED PYRIDOPSORALEN

It has been recently shown that UVA (320-400 nm) irradiation of DNA in the presence of pyridopsoralens induces the formation of thymine cycl obutane dimers in addition to monoadducts. In this work, we measured t he potency of a saturated pyridopsoralen to photosensitize DNA, despit e its inability to covalently attach to DNA. First, from spectroscopic fluorescence measurements, we have shown that both analogs, saturated and unsaturated pyridopsoralens, namely 4',5'-dihydro-7-methylpyrido[ 3,4-c]psoralen (DH-MePyPs) and 7-methylpyrido[3,4-c]psoralen, exhibit a similar global affinity for DNA. Secondly, we demonstrated, by footp rinting experiments, that exposure of a DNA sequence to 365 nm UV radi ation in the presence of DH-MePyPs results in selective cyclobutane th ymine dimerization. Thymines located in the immediate proximity of the 5'-TA-3' step are exclusively affected and the frequency of this phot oprocess depends on flanking sequences. We thus probe a selective thym ine dimer photosensitizer. Results are discussed in terms of drug affi nity and physical properties of the helix at the binding site.