Probing DNA Radiation Damage by DNA Nanotechnology

• Applicant: Professor Dr. Ilko Bald
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry ; Physical Chemistry of Solids and Surfaces, Material Characterisation
• Term: from 2012 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 230710387

• Final Report Year: 2020

Final Report Abstract

When biological tissue is irradiated with high energy radiation, water molecules are ionized in a first step resulting in a cascade of low energy electrons (with an energy typically below 20 eV). The research of the past 20 years had shown that secondary electrons are responsible for much of the radiation damage in biological tissue. In this context the damage of the DNA, as the carrier of the genetic information, is of special importance. The aim of the project was to obtain an in-depth understanding of the dependency of DNA damage on the sequence and investigate whether electron induced DNA damage occurs in an aqueous environment (like it is present in biological cells). In order to tackle these two issues, new methods based on DNA origami nanostructures and metallic nanoparticles, respectively, have been developed and applied. Target DNA sequences positioned on DNA origami nanoplatforms have been irradiated with electrons with a well-defined energy. Using atomic force microscopy, the absolute amount of radiation induced strand breaks could be quantified and the dependency on the DNA sequence and the electron energy could be investigated. We figured out that strand breaks are preferably generated by electrons with an energy around 7 eV in all investigated sequences, which is indicating the underlying reaction mechanism, namely the initial formation of anionic resonances by electron attachment at this energy. Some sequences have an additional maximum around 10 eV and double strand breaks are favorably generated at 10 eV as well. The differences between the sequences are rather low, whereas there are some specific sequences, which are very sensitive towards low energy secondary electrons, like the guanine rich telomer sequence, which is located at the end of the chromosomes with several repeat units and which length determines the life time of a cell. The results of this study have been featured in ChemistryViews (https://www.chemistryviews.org/details/ ezine/10934136/Low-Energy_Electrons_Cause_DNA_Strand_Breaks.html). High energy radiation is used in cancer radiation therapy to reduce tumor tissue in a targeted manner. In this project we could elucidate the role of so-called radiosensitizers, which can be incorporated into the DNA to make the tumor tissue more sensitive towards irradiation. We could show that the incorporation of halogenated nucleotides into the DNA could nearly double the electron induced strand breaks, which clearly demonstrates that the mode of action of these therapeutics is based on their interaction with low energy electrons. These insights into the radiosensitization mechanisms combined with the newly developed DNA origami based quantification of radiation induced DNA strand breaks in specific sequences allows a targeted development of new radiosensitizers with improved properties.

Publications

• Decomposition of DNA nucleobases by laser irradiation of gold nanoparticles monitored by surface-enhanced Raman scattering; J. Phys. Chem. C 2016,120, 3001
  R. Schürmann, I. Bald
  
• Sensitizing DNA Towards Low-Energy Electrons with 2-Fluoroadenine; Angew. Chem. Int. Ed. 2016, 55, 10248
  J. Rackwitz, J. Kopyra, I. Dabkowska, K. Ebel, M. Lj. Rankovic, A. R. Milosavljevic, I. Bald
  
• A novel setup for the determination of absolute cross sections for lowenergy electron induced strand breaks in oligonucleotides – The effect of the radiosensitizer 5-fluorouracil; Eur. Phys. J. D 2017, 71, 32
  J. Rackwitz, M. Lj. Rankovic, A. R. Milosavljevic, I. Bald
  
• Dissociative Electron Attachment to Biomolecules, in: Nanoscale Insights into Ion-Beam Cancer Therapy, Ed.: A. Solov'yov, Springer 2017
  I. Bald, R. Curik, J. Kopyra, M. Tarana
  
• Effect of adsorption kinetics on dissociation of DNA-nucleobases on gold nanoparticles under pulsed laser illumination; Phys. Chem. Chem. Phys. 2017,19, 10796
  R. Schürmann, I. Bald
  
• Real-time monitoring of plasmon induced dissociative electron transfer to the potential DNA radiosensitizer 8-bromoadenine; Nanoscale 2017, 9, 1951
  R. Schürmann, I. Bald
  
• Resonant formation of strand breaks in sensitized oligonucleotides induced by low-energy electrons (0.5 - 9.0 eV); Angew. Chem. Int. Ed. 2017, 56, 10952
  R. Schürmann, T. Tsering, K. Tanzer, S. Denifl, S. V. K. Kumar, I. Bald
  
• Stability of the Parent Anion of the Potential Radiosensitizer 8-Bromoadenine Formed by Low-Energy (<3 eV) Electron Attachment; J. Phys. Chem. B 2017, 121, 5730
  R. Schürmann, K. Tanzer, I. Dabkowska, S. Denifl, I. Bald
  
• Low-Energy Electron-Induced Strand Breaks in Telomere-Derived DNA Sequences - Influence of DNA Sequence and Topology, Chem. Eur. J. 2018, 24, 4680
  J. Rackwitz, I. Bald
  
• The physico-chemical basis of DNA radiosensitization - Implications for cancer radiation therapy, Chem. Eur. J. 2018, 24, 10271
  R. Schürmann, S. Vogel, K. Ebel
  
• Electron-Induced Reaction in 3-Bromopyruvic Acid, Chem. Eur. J. 2019, 25, 5498-5506
  F. Ferreira da Silva, M. Varella, N. Jones, S. Hoffmann, S. Denifl, I. Bald and J. Kopyra
  
• Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA; Int. J. Mol. Sci. 2020, 21, 111
  K. Ebel, I. Bald