title: H-NMR studies of duplex DNA decamer containing a uracil cyclobutane dimer: implications regarding the high UV mutagenecity of CC photolesions.
abstract: To determine the origin of the UV-specific CC to TT tandem mutation at the CC site, we made a duplex DNA decamer containing a uracil cis-syn cyclobutane dimer (CBD) as the deaminated model of a cytosine dimer. Two-dimensional 1H-NMR spectroscopy studies were performed on this sequence where two adenines (Ade) were opposite to the uracil dimer. Two imino protons of the uracil dimer were found to retain Watson-Crick hydrogen bonding with the opposite Ade, although the 5'-U(NH) of the dimer site showed unusual upfield shift like that of the 5'-T(NH) of the TT dimer, which seemed to be associated with deshielding by the flanking base rather than with reduced hydrogen bonding. (McAteer et al. 1998, J. Mol. Biol. 282:1013-1032). Hydrogen bondings at the dimer site were also supported by detecting typical strong nuclear Overhauser effects (NOE) between two imino protons and the opposite Ade H2 or NH2. But sequential NOE interactions of base protons with sugar protons were absent at the two flanking nucleotides of the 5' side of the uracil dimer and at the intradimer site, contrasting with its thymine analog where sequential NOE was absent only at the A4-T5 step. In addition, NOE cross peak for U5(NH) <--> A4(H2) was detected, although the NOE interactions of U6(NH) with A7(H2) and A17(H2) were not observed in contrast to the thymine dimer duplex. This different local structural alteration may be affected by the induced right-hand twisted puckering mode of cis-syn cyclobutane ring of the uracil dimer in the B-DNA duplex, even though the isolated uracil dimer had left-hand twisted puckering rigidly. In parallel, these observations may be correlated with observed differences in mutagenic properties between cis-syn UU dimer and cis-syn TT dimer.
authors.affiliation: Department of Chemistry, Yeungnam University, Taegu, South Korea.
authors.forename: Hyun Mee
authors.initials: HM
authors.lastname: Lee
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects; D004249:DNA Damage; D006860:Hydrogen Bonding; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011522:Protons; D011740:Pyrimidine Dimers / Q000032:analysis*; D014466:Ultraviolet Rays; D014498:Uracil / Q000032:analysis*
chemical_list: D011522:Protons; D011740:Pyrimidine Dimers; D014498:Uracil; D004247:DNA