Quantifying aspects of DNA damage

The exposure of deoxyribonucleic acid, DNA, to radiation is known to result in damage, which can lead to variety of biological consequences including disruptions in genetic function and even cancer. Various aspects of DNA damage resulting from exposure to ultraviolet (UV) radiation and ionizing radiation have been explored and quantified. The most common source of UV radiation is sunlight, however the risk associated with wavelength and dose dependent sunlight exposure and the development of melanoma is not clearly defined. A small electronic device, a dosimeter, has been developed that can directly monitor the extent of UV exposure within a specific wavelength range and thus provide a tool to assess the biological risks and consequences incurred from quantified doses of sunlight. Further, a narrowband, tunable laser source has been used to determine the correlation between the wavelength specific UV irradiation of genomic DNA and the incidence of photolesion formation. Carefully calibrated irradiation wavelengths and doses ensure the data may serve as a benchmark for future wavelength specific DNA damage studies.;In an effort to define the energetic threshold for DNA and DNA component ionization, liquid-jet photoelectron spectroscopy has been used to study the vertical ionization energies of DNA and RNA constituents in their native aqueous environment. The experimental investigation of purine and pyrimidine nucleotides, as well as their individual components, demonstrate that photoelectron spectra of DNA and RNA bases consist of a linear combination of the spectra of their individual chemical components. Furthermore, the aid of theory has allowed the assignment of the first vertical transition in all investigated nucleosides and nucleotides to a single transition centered solely on the nucleobase. Combining the experimentally determined vertical ionization energies with theoretically determined reorganization energies has allowed for the spectroscopic determination of the one-electron oxidation energy of each investigated biomolecule. The impact of higher order structure resulting from base stacking and hydrogen bonding has been investigated using G-quartets formed in highly concentrated solutions of 5'-guanosine monophosphate. No distinguishable changes were observed in the vertical ionization energies of solutions containing higher order structures and those that did not. The liquid-jet technique was further used to obtain the first photoelectron spectrum of double stranded DNA. The noncovalent interactions of base pairing and base stacking in helical DNA do not result in any significant shifts in the lowest vertical ionization energy as compared to a solution of equimolar concentrations of the nucleic acid nucleotides AMP, CMP, GMP, and UMP. Taken together with the GMP quartet findings suggests that higher order structure does not appear to have a large impact on the first vertical ionization energy.