Elucidating DNA damage and repair processes by independently generating reactive and metastable intermediates

DNA damage is a double-edged sword. The modifications produced in the biopolymer are associated with aging, and give rise to a variety of diseases, including cancer. DNA is also the target of anti-tumor agents and the most generally used nonsurgical treatment of cancer, ionizing radiation. Agents that damage DNA produce a variety of radicals. Elucidating the chemistry of individual DNA radicals is challenging due to the availability of multiple reactive pathways and complexities inherent with carrying out mechanistic studies on a heterogeneous polymer. The ability to independently generate radicals and their metastable products at defined sites in DNA has greatly facilitated understanding this biologically important chemistry.