Probing DNA Radiation Damage by DNA Nanotechnology (NANORADAM)
Probing DNA Radiation Damage by DNA Nanotechnology
Start date: Apr 1, 2013,
End date: Mar 31, 2017
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 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 be determined as a function of the electron energy using the DNA origami technique combined with atomic force microscopy. Furthermore, the DNA origami technique allows for the study of the influence of an aqueous environment on the DNA strand break yield. The final goal is to identify the DNA target structures that can be most efficiently sensitized to low-energy electrons by radiosensitizers. This fundamental knowledge will have important implications for the development of novel therapeutics and the improvement of radiation cancer therapy.
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