Highly efficient photochemical 2'-deoxyribonolactone formation at the diagonal loop of a 5-lodouracil-containing antiparallel G-quartet

To explore the structure-dependent hydrogen abstraction in antiparallel and parallel G-quartet DNA structures, the photochemical reactivity of 5-iodouracil (U-1)-containing human telomeric DNA 22-mers was investigated under the 302 nm UV irradiation conditions. We discovered that only antiparallel ODN 4, in which the second T residue in the diagonal loop of the antiparallel G-quartet is substituted with U-1, was rapidly consumed as compared with parallel ODN 4 and the other U-1-containing 22-mers under the irradiation conditions. Product analysis of the photolyzate of antiparallel ODN 4 indicated that a 2'-deoxyribonolactone residue was effectively produced at the 5' side of the U-1 residue in the diagonal loop. Photochemical 2'deoxyribonolactone formation was also found in the U-1-containing diagonal loop of antiparallel G-quartets d(GGGGTTT(1)UGGGG)(2) and d(GGGGTT(1)UTGGGG)(2), whereas the reaction did not occur at other DNA structures, including the single-stranded form, the loop region of the hairpin, and linear four-stranded G-quartets. The results clearly indicate that this type of 2'-deoxyribonolactone formation efficiently occurrs only in the diagonal loop of the antiparallel G-quartet. Furthermore, we found that 2'-deoxyribonolactone was formed at the U-1-containing G-rich sequence of the IgG switch regions and the 5' termini of the Rb gene, suggesting the formation of an antiparallel G-quartet with a diagonal loop in these sequences. These results suggest that the present photochemical method can be used as a specific probe for the antiparallel G-quartet with the diagonal loop.