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DNA radiation damage probed by DNA nanotechnology

Overview

DNA origami triangle with six streptavidin modifications
Photo: Dr. Jenny Rackwitz

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.
We have developed a novel DNA origami technique to map the radiation damage of different and complex DNA target structures with unprecedented efficiency and accuracy. A two-dimensional DNA origami template functionalized with protruding well-defined DNA structures is exposed to a beam of low-energy electrons or photons. The strand break yield of different nucleotide sequences is then determined as a function of the electron or photon energy using atomic force microscopy.
Furthermore, we aim at identifying the DNA target structures that can be most efficiently sensitized to low-energy electrons by radiosensitizers, which are used to treat cancer, and we study DNA strand breakage by singlet oxygen.

DNA origami triangle with six streptavidin modifications
Photo: Dr. Jenny Rackwitz

Selected publications

Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA K. Ebel & I. Bald Int. J. Mol. Sci. 2020, 21, 111.

Vacuum-UV and Low-Energy Electron Induced DNA Strand Breaks – Influence of the DNA Sequence and Substrate, S. Vogel, K. Ebel, R. Schürmann, C. Heck, T. Meiling, A. Milosavljević, A. Giuliani, I. Bald, ChemPhysChem 2019, 20, 823-830. Cover: 10.1002/cphc.201900204.

Vacuum-UV induced DNA strand breaks - influence of the radiosensitizers 5-bromouracil and 8-bromoadenine, S. Vogel, K. Ebel, C. Heck, R. Schürmann, A. Milosavljević, A. Giuliani, I. Bald, Phys. Chem. Chem. Phys., 2019, 21, 1972.

The Physico-Chemical Basis of DNA Radiosensitization: Implications for Cancer Radiation Therapy R. Schürmann, S. Vogel, K. Ebel & I. Bald Chem. Eur. J. 2018, 24, 10271-10279.

Low-Energy Electron-Induced Strand Breaks in Telomere-Derived DNA Sequences - Influence of DNA Sequence and Topology, J. Rackwitz, I. Bald, Chem. Eur. J. 2018, 24, 4680. See also a feature article in Chemistry Views.

Resonant formation of strand breaks in sensitized oligonucleotides induced by low-energy electrons (0.5 - 9.0 eV); R. Schürmann, T. Tsering, K. Tanzer, S. Denifl, S. V. K. Kumar, I. Bald, Angew. Chem. Int. Ed. 2017, 56, 10952.

A novel setup for the determination of absolute cross sections for low-energy electron induced strand breaks in oligonucleotides – The effect of the radiosensitizer 5-fluorouracil; J. Rackwitz, M. Lj. Rankovic, A. R. Milosavljevic, I. Bald, Eur. Phys. J. D 2017, 71, 32.

Sensitizing DNA Towards Low-Energy Electrons with 2-Fluoroadenine; J. Rackwitz, J. Kopyra, I. Dabkowska, K. Ebel, M. Lj. Rankovic, A. R. Milosavljevic, I. Bald, Angew. Chem. Int. Ed. 2016, 55, 10248.

Using DNA Origami Nanostructures To Determine Absolute Cross Sections for UV Photon-Induced DNA Strand Breakage; S. Vogel, J. Rackwitz, R. Schürman, J. Prinz, A. R. Milosavljević, M. Réfrégiers, A. Giuliani, I. Bald, J. Phys. Chem. Lett. 2015, 6, 4589.