Interaction of Vacuum UV radiation (6 - 12 eV) with complex DNA targets

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The interaction of UV radiation with living organisms can lead for instance to mutations within the genome. The photophysics associated with the lowest pi-pi* transition (around 4.8 eV or 260 nm) in DNA nucleobases, which can result for example in the formation of thymine dimers, was studied in great detail during the last 10 - 15 years. The excitation of DNA at energies as low as 6 eV can already result in DNA strand breaks, which become the dominant form of DNA radiation damage at photon energies above the ionization threshold (> 8 - 9 eV). However, the processes leading to DNA strand breaks are barely explored. The aim of the present proposal is a detailed characterization of the excitation/ionization below and right above the ionization threshold of the DNA nucleobases (6 - 12 eV) and the quantification of the resulting DNA strand breakage. Oligonucleotides with well-defined sequences up to about 15 nucleotides will be studied both experimentally and theoretically to reveal the influence of DNA sequence and local environment on the vacuum UV (VUV) photon-induced DNA strand breakage. To approach this problem, the absolute cross sections for DNA strand breakage will be determined as a function of nucleotide sequence and photon energy using synchrotron radiation. A recently developed DNA origami based technique will be used to provide the target oligonucleotides, while analysis by atomic force microscopy (AFM) enables the determination of strand break cross sections. To further explore the mechanism of the photo-induced DNA strand breakage and its sequence dependence, the ionization potential (IP) of the respective DNA sequences will be determined by irradiation of gas phase oligonucleotide ions with synchrotron radiation in the VUV range in a tandem mass spectrometry setup. In parallel the IPs of oligonucleotides will be determined computationally using state-of-the-art electronic structure methods. Additionally, the ionization cross sections and the relative stability of ionized DNA stacks will be calculated from first principles. The joint experimental and theoretical approach will reveal the influence of DNA primary and secondary structure and environment on DNA excitation, ionization and strand breakage. The applied innovative methods and the obtained results can contribute to an optimization of tumor radiation therapy and will have implications also for related fields such as DNA charge transport.