Probing DNA Structure by Photoelectron Transter and Its Application toward Gene The rapy

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DNA conformation plays an important role in nearly every aspect of DNA function, including DNA replication, gene expression and regulation. Understanding DNA conformation and its role in biological processes is intense current interest and it will be a valuable information in designing new anticancer and gene-thepeutic agents. The aim of this research is to evaluate the potential of 5-halouracil photoreaction as DNA local conformational analysis and conformation-specific DNA cleaving agent. It was found that photoiradiation of bromouracil (BrU) -containing oligonucleotide efficiently produces deoxyribose 1' oxidation product at adenine residue of ABrU Sequence, while iodoracil (IU) -containing oligomer produces comparable amount of 1' and 2' oxidation products. Detailed mechanism of oxidative DNA strand scission including 1,2-hydride shift in the formation of 1' oxidation product was elucidated. ABrU photochemical unit was introduced into various type of DNA conformations. It was found that A conformation enhanced efficiency of the reaction and specificity of 1' oxidation was increased. Introduction of mismatch at adenine site does not change the photoreactivity whereas introduction of mismatch at BrU site greatly reduced photoreactivity.