Free radicals are powerful but in some instances indiscriminate nucleic acid damaging agents. This is especially true with respect to the radicals produced by ionizing radiation (e.g. g-radiolysis), which generates reactive species within nucleic acids directly and through the intermediacy of reactive oxygen species (e.g. hydroxyl radical). The complexity of radiation-induced damage is increased due to the heterogeneous structure of nucleic acids combined with the wrapping of nuclear DNA around the octameric core of histone proteins.Our research group studies radical induced nucleic acid damage using organic chemistry to independently generate the products and reactive intermediates that are produced. When combined with solid phase oligonucleotide synthesis and enzyme ligation, we are able to independently generate DNA lesions and reactive intermediates at defined sites within free nucleic acids and within nucleosomes. This approach greatly simplifies studying the effects of ionizing radiation on nucleic acids and has enabled us to test reaction mechanisms and uncover unrecognized chemistry in RNA, as well as free and nucleosomal DNA. Recent efforts in this area will be presented.

Free radical mediated nucleic acid damage

244th National Meeting (2012)

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