Photochemical probe of DNA local structures

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DNA is polymorphic and exists in a variety of distinct conformations. Duplex DNA can adopt a variety of sequence-dependent secondary structures, which range from the canonical right-handed B form through to the left-handed Z form. However, the biological roles associated with the different structural conformations of DNA are not well understood because of the short lifetime of appearance of each structure and the difficulty in creating a system to demonstrate the DNA local structure. We found that incorporation of 8-methyl-2'-deoxyguanosine (m8G) and 8-methylguanosine (m8rG) into DNA dramatically stabilized the Z form, and facilitated the B-Z transition, even for AT-containing sequences. Developing a Z-stabilizing monomeric unit, the Z stabilizer, allowed us to understand the solution structure of Z-DNA and to reveal the specific 2'β-hydrogen abstraction that gives rise to the Z-form-specific 2'α-hydroxylation of the 5-halouracil-containing Z-form under UV irradiation. We also investigated the photoreaction of 5-halouracil in the A-form, B-form, G-quartet, and protein-induced DNA kinks. Hydrogen abstraction by 2'-deoxyuridin-5-yl generated from 5-halouracil under irradiation was atom specific and highly dependent on the DNA structure.