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Consecutive Adenine Sequences Serve as Potential Targets in Photosensitized Oxidative DNA Damage (pp. 221-235) $100.00
Authors:  (Kiyohiko Kawai, The Institute of Scientific and Industrial Research, Osaka University, Tetsuro Majima, The Institute of Scientific and Industrial Research, Japan)
Abstract:
Upon exposure of our skin to solar UV radiation, the photosensitized DNA damage
takes place through two major pathways, i.e., formation of the mutagenic pyrimidine
dimmers via excitation of the pyrimidine bases, and one-electron oxidation of
nucleobases triggered by electron transfer from the nucleobase to the excited
photosensitizer. This chapter shed light on the latter process. In the initial step of the
photosensitized DNA damage by one-electron oxidation, a positive charge “a hole” is
generated in DNA which can subsequently migrate along DNA. Though a number of
kinetic and theoretical studies have been performed, the biological relevance between the
charge transfer in DNA and photosensitized DNA damage are still not clear. Herein, the
kinetic mechanisms of the photosensitized one-electron oxidation of DNA was assayed
both by the direct spectroscopic measurements of the charge transfer in DNA and by
quantification of the yield of the guanine oxidative damage. Consecutive adenine
sequences were found to be a good launching site for the photosensitizers to inject a hole
in DNA, where the following rapid hole transfer through adenines causes a long-lived
charge-separated state leading to DNA oxidative damage. It was clearly demonstrated
that the consecutive adenine sequences serve as a good target in the photosensitized
DNA damage, or G adjacent to such sequences may be a potential hot spot of oxidative
DNA damage. The essential requisites for the efficient and/or harmful photosensitizer are
given as follows: be able to oxidize adenine, and react rapidly with molecular oxygen
following its reduction avoiding the charge recombination and making the reaction
irreversible. Elucidation of the kinetic mechanisms of the photosensitized one-electron
oxidation of DNA allowed us to know the effective target DNA sequences and the
essential requisites for the efficient photosensitizer, which will greatly help the
understanding of the harmful compound for health and the improvement of the
photosensitizer for therapeutic and biochemical applications. 


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Consecutive Adenine Sequences Serve as Potential Targets in Photosensitized Oxidative DNA Damage (pp. 221-235)