Solid State 2H NMR Analysis of Furanose Ring Dynamics in DNA Containing Uracil

DNA damage has been implicated in numerous human diseases, particularly cancer, and the aging process. Single-base lesions, Such as Uracil, in DNA can be cytotoxic or mutagenic and are recognized by a DNA glycosylase during the process of base excision repair. Increased dynamic properties in lesion-containing DNAs have been Suggested to assist recognition and specificity. Deuterium solid-state nuclear magnetic resonance (SSNMR) has been used to directly observe local dynamics of the furanose ring within a uracil: adenine (U:A) base pair and compared to a normal thymine:adenine (T:A) base pair. Quadrupole echo lineshapes, < T-IZ >, and < T-2e > relaxation data were collected, and computer modeling was performed. The results indicate that the relaxation times are identical within the experimental error, the solid lineshapes are essentially indistinguishable above the noise level, and our lineshapes are best fit with a model that does not have significant local motions. Therefore, U:A base pair furanose rings appear to have essentially identical dynamic properties as a normal T:A base pair, and the local dynamics of the furanose ring are unlikely to be the sole arbiter for uracil recognition and specificity in U:A base pairs.