@phdthesis{Vogel2018,
  author    = {Vogel, Stefanie},
  title     = {Sequence dependency of photon and electron induced DNA strand breaks},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-419669},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xii, 117},
  year      = {2018},
  abstract  = {Deoxyribonucleic acid (DNA) is the carrier of human genetic information and is exposed to environmental influences such as the ultraviolet (UV) fraction of sunlight every day. The photostability of the DNA against UV light is astonishing. Even if the DNA bases have a strong absorption maximum at around 260 nm/4.77 eV, their quantum yield of photoproducts remains very low 1. If the photon energies exceed the ionization energy (IE) of the nucleobases ( ̴ 8-9 eV) 2, the DNA can be severely damaged. Photoexcitation and -ionization reactions occur, which can induce strand breaks in the DNA. The efficiency of the excitation and ionization induced strand breaks in the target DNA sequences are represented by cross sections. If Si as a substrate material is used in the VUV irradiation experiments, secondary electrons with an energy below 3.6 eV are generated from the substrate. This low energy electrons (LEE) are known to induce dissociative electron attachment (DEA) in DNA and with it DNA strand breakage very efficiently. LEEs play an important role in cancer radiation therapy, since they are generated secondarily along the radiation track of ionizing radiation. In the framework of this thesis, different single stranded DNA sequences were irradiated with 8.44 eV vacuum UV (VUV) light and cross sections for single strand breaks (SSB) were determined. Several sequences were also exposed to secondary LEEs, which additionally contributed to the SSBs. First, the cross sections for SSBs depending on the type of nucleobases were determined. Both types of DNA sequences, mono-nucleobase and mixed sequences showed very similar results upon VUV radiation. The additional influence of secondarily generated LEEs resulted in contrast in a clear trend for the SSB cross sections. In this, the polythymine sequence had the highest cross section for SSBs, which can be explained by strong anionic resonances in this energy range. Furthermore, SSB cross sections were determined as a function of sequence length. This resulted in an increase in the strand breaks to the same extent as the increase in the geometrical cross section. The longest DNA sequence (20 nucleotides) investigated in this series, however, showed smaller cross section values for SSBs, which can be explained by conformational changes in the DNA. Moreover, several DNA sequences that included the radiosensitizers 5-Bromouracil (5BrU) and 8-Bromoadenine (8BrA) were investigated and the corresponding SSB cross sections were determined. It was shown that 5BrU reacts very strongly to VUV radiation leading to high strand break yields, which showed in turn a strong sequence-dependency. 8BrA, on the other hand, showed no sensitization to the applied VUV radiation, since almost no increase in strand breakage yield was observed in comparison to non-modified DNA sequences. In order to be able to identify the mechanisms of radiation damage by photons, the IEs of certain DNA sequences were further explored using photoionization tandem mass spectrometry. By varying the DNA sequence, both the IEs depending on the type of nucleobase as well as on the DNA strand length could be identified and correlated to the SSB cross sections. The influence of the IE on the photoinduced reaction in the brominated DNA sequences could be excluded.},
  language  = {en}
}