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DNA radiation damage probed by DNA nanotechnology

Low-energy electron induced reactions

DNA double helix irradiated by electrons.

In cancer radiation therapy predetermined doses of high-energy radiation are administered to reduce tumours. More than 60 % of the patients diagnosed with cancer are treated with radiation therapy. A detailed understanding of the fundamental mechanisms of DNA radiation damage is of utmost importance with respect to the question of how the damage can be increased by therapeutics used in radiation therapy. On a molecular level a large extent of the cell damage is ascribed to the production of secondary low-energy electrons along the high-energy radiation track that induce DNA single and double strand breaks. The physico-chemical mechanisms of DNA radiation damage can currently only be described for idealized small model systems (such as individual nucleobases) and it is not known, which DNA nucleotide sequences and higher-order DNA structures are most susceptible to damage. Very recent ground-breaking advances in DNA nanotechnology allow for the first time the detailed study of the interaction of radiation with complex DNA structures. With an innovative DNA origami technique it is possible to map the radiation damage of different DNA target structures with unprecedented efficiency and accuracy. A two-dimensional DNA origami template functionalized with protruding well-defined DNA structures will be exposed to a beam of low-energy electrons. The strand break yield of different nucleotide sequences will then be determined as a function of the electron energy using atomic force microscopy. The final goal is to identify the DNA target structures that can be most efficiently sensitized to low-energy electrons by radiosensitizers. 

J. Rackwitz, I. Bald, Chem. Eur. J. 2018, DOI: 10.1002/chem.201705889.

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VUV induced reactions

We have characterized ultraviolet (UV) photon-induced DNA strand break processes by determination of absolute cross sections for photoabsorption and for sequence-specific DNA single strand breakage induced by photons in an energy range from 6.50 to 8.94 eV. These represent the lowestenergy photons able to  induce DNA strand breaks. Oligonucleotide targets are immobilized on a UV transparent substrate in controlled quantities throughattachment to DNA origami templates. Photon-induced dissociation of single DNA strands is visualized and quantified using atomic force microscopy. The obtained quantum yields for strand breakage vary between 0.06 and 0.5, indicating highly efficient DNA strand breakage by UV photons, which is clearly dependent on the photon energy. Above the ionization threshold strand breakage becomes clearly the dominant form of DNA radiation damage, which is then also dependent on the nucleotide sequence.

S. Vogel, J. Rackwitz, R. Schürman, J. Prinz, A. R. Milosavljević, M. Réfrégiers, A. Giuliani, I. Bald, J. Phys. Chem. Lett. 20156, 4589.