Excited electronic states of nucleic acids and other biological molecules are the precursors of virtually all forms of radiation damage to the genetic material. These precursor states are poorly understood at present because they are extremely short-lived at physiological temperatures, with lifetimes on the order of 10-13 to 10-11 s. The research proposed will use state-of-the-art ultrafast methods to directly study the nucleic acid states excited by ultraviolet light which lead to damage sties on the nucleotide helix. The goals are to determine how the excitation/damage process depends upon base content and conformation of the helix, how helix intercalating agents can intercept energy deposited on the helix and dissipate the energy without nucleotide damage, and why most of the damage sites seems to involve pyrimidine dimers and adducts. The primary methods to be used are time- and wavelength-resolved absorption and fluorescence spectroscopy using well-defined synthetic nucleotide oligomers and polymers designed to answer specific questions concerning damage mechanisms. These studies will for the first time directly probe the time evolution of the major energetic events caused by ultraviolet light absorption and will quantitate rates and routes of energy disposition in DNA which leads to base damage.
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