Tandem Lesions Are the Major Products Resulting from a Pyrimidine Nucleobase Radical

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Abstract
Nucleobase radicals (e.g., 1) are the major family of reactive intermediates formed when DNA is exposed to γ-radiolysis. Independent generation of 1 in chemically synthesized oligonucleotides reveals that formation of this nucleobase radical under aerobic conditions results in the formation of tandem lesions approximately 65% of the time. The distribution of lesions formed with the 5‘- and 3‘-adjacent nucleotides is dependent upon the secondary structure of duplex DNA. Tandem lesions, which are defined as two contiguously, damaged nucleotides in a single DNA strand, are of significant biological interest. The yield of tandem lesions from 1 is much greater than was previously believed. The observations presented could have significant ramifications on how scientists interpret the effects of γ-radiolysis on DNA.