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 cyclobutane dimers in addition to monoadducts. In this work, we measured the potency of a saturated pyridopsoralen to photosensitize DNA, despite 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-methyl-pyrido[3,4-c]psoralen (DH-MePyPs) and 7-methylpyrido[3,4-c]psoralen, exhibit a similar global affinity for DNA. Secondly, we demonstrated, by footprinting experiments, that exposure of a DNA sequence to 365 nm UV radiation in the presence of DH-MePyPs results in selective cyclobutane thymine dimerization. Thymines located in the immediate proximity of the 5'-TA-3' step are exclusively affected and the frequency of this photoprocess depends on flanking sequences. We thus probe a selective thymine dimer photosensitizer. Results are discussed in terms of drug affinity and physical properties of the helix at the binding site.
Guillo
L A
LA
Laboratoire de Physique et Chimie Biomoléculaires, Institut Curie, Paris, France.
Blais
J
J
Vigny
P
P
Spassky
A
A
D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D011564:Furocoumarins / Q000737:chemistry / Q000528:radiation effects; D008969:Molecular Sequence Data; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000528:radiation effects*; D014466:Ultraviolet Rays
D011564:Furocoumarins; D017319:Photosensitizing Agents; D011740:Pyrimidine Dimers; D004247:DNA