TY - JOUR A1 - Rackwitz, Jenny A1 - Bald, Ilko T1 - Low-energy electron-induced strand breaks in telomere-derived DNA sequences BT - influence of DNA sequence and topology JF - Chemistry - a European journal N2 - During cancer radiation therapy high-energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low-energy (<20 eV) electrons, which are able to damage DNA very efficiently by dissociative electron attachment. Recently, it was suggested that low-energy electron-induced DNA strand breaks strongly depend on the specific DNA sequence with a high sensitivity of G-rich sequences. Here, we use DNA origami platforms to expose G-rich telomere sequences to low-energy (8.8 eV) electrons to determine absolute cross sections for strand breakage and to study the influence of sequence modifications and topology of telomeric DNA on the strand breakage. We find that the telomeric DNA 5′-(TTA GGG)2 is more sensitive to low-energy electrons than an intermixed sequence 5′-(TGT GTG A)2 confirming the unique electronic properties resulting from G-stacking. With increasing length of the oligonucleotide (i.e., going from 5′-(GGG ATT)2 to 5′-(GGG ATT)4), both the variety of topology and the electron-induced strand break cross sections increase. Addition of K+ ions decreases the strand break cross section for all sequences that are able to fold G-quadruplexes or G-intermediates, whereas the strand break cross section for the intermixed sequence remains unchanged. These results indicate that telomeric DNA is rather sensitive towards low-energy electron-induced strand breakage suggesting significant telomere shortening that can also occur during cancer radiation therapy. KW - DNA damage KW - DNA strand breaks KW - low-energy electron KW - radiation therapy KW - telomeric DNA Y1 - 2018 U6 - https://doi.org/10.1002/chem.201705889 SN - 0947-6539 SN - 1521-3765 VL - 24 IS - 18 SP - 4680 EP - 4688 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Vogel, Stefanie A1 - Ebel, Kenny A1 - Schürmann, Robin Mathis A1 - Heck, Christian A1 - Meiling, Till A1 - Milosavljevic, Aleksandar R. A1 - Giuliani, Alexandre A1 - Bald, Ilko T1 - Vacuum-UV and Low-Energy Electron-Induced DNA Strand Breaks BT - Influence of the DNA Sequence and Substrate JF - ChemPhysChem : a European journal of chemical physics and physical chemistry N2 - DNA is effectively damaged by radiation, which can on the one hand lead to cancer and is on the other hand directly exploited in the treatment of tumor tissue. DNA strand breaks are already induced by photons having an energy below the ionization energy of DNA. At high photon energies, most of the DNA strand breaks are induced by low-energy secondary electrons. In the present study we quantified photon and electron induced DNA strand breaks in four different 12mer oligonucleotides. They are irradiated directly with 8.44 eV vacuum ultraviolet (VUV) photons and 8.8 eV low energy electrons (LEE). By using Si instead of VUV transparent CaF2 as a substrate the VUV exposure leads to an additional release of LEEs, which have a maximum energy of 3.6 eV and can significantly enhance strand break cross sections. Atomic force microscopy is used to visualize strand breaks on DNA origami platforms and to determine absolute values for the strand break cross sections. Upon irradiation with 8.44 eV photons all the investigated sequences show very similar strand break cross sections in the range of 1.7-2.3x10(-16) cm(2). The strand break cross sections for LEE irradiation at 8.8 eV are one to two orders of magnitude larger than the ones for VUV photons, and a slight sequence dependence is observed. The sequence dependence is even more pronounced for LEEs with energies <3.6 eV. The present results help to assess DNA damage by photons and electrons close to the ionization threshold. KW - DNA origami KW - DNA radiation damage KW - DNA strand breaks KW - low-energy electrons KW - vacuum-UV radiation Y1 - 2019 U6 - https://doi.org/10.1002/cphc.201801152 SN - 1439-4235 SN - 1439-7641 VL - 20 IS - 6 SP - 823 EP - 830 PB - Wiley-VCH CY - Weinheim ER - TY - GEN A1 - Ebel, Kenny A1 - Bald, Ilko T1 - Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, which are able to induce DNA strand breaks via dissociative electron attachment. Absolute DNA strand break cross sections of specific DNA sequences can be efficiently determined using DNA origami nanostructures as platforms exposing the target sequences towards LEEs. In this paper, we systematically study the effect of the oligonucleotide length on the strand break cross section at various irradiation energies. The present work focuses on poly-adenine sequences (d(A₄), d(A₈), d(A₁₂), d(A₁₆), and d(A₂₀)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. When going from d(A₄) to d(A₁₆), the strand break cross section increases with oligonucleotide length, but only at 7.0 and 8.4 eV, i.e., close to the maximum of the negative ion resonance, the increase in the strand break cross section with the length is similar to the increase of an estimated geometrical cross section. For d(A₂₀), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA₂₀ sequence. The results indicate that, although there is a general length dependence of strand break cross sections, individual nucleotides do not contribute independently of the absolute strand break cross section of the whole DNA strand. The absolute quantification of sequence specific strand breaks will help develop a more accurate molecular level understanding of radiation induced DNA damage, which can then be used for optimized risk estimates in cancer radiation therapy. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 814 KW - DNA origami KW - DNA radiation damage KW - DNA strand breaks KW - low-energy electrons KW - sequence dependence Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-444125 SN - 1866-8372 IS - 814 ER - TY - JOUR A1 - Ebel, Kenny A1 - Bald, Ilko T1 - Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA JF - International Journal of Molecular Sciences N2 - The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, which are able to induce DNA strand breaks via dissociative electron attachment. Absolute DNA strand break cross sections of specific DNA sequences can be efficiently determined using DNA origami nanostructures as platforms exposing the target sequences towards LEEs. In this paper, we systematically study the effect of the oligonucleotide length on the strand break cross section at various irradiation energies. The present work focuses on poly-adenine sequences (d(A₄), d(A₈), d(A₁₂), d(A₁₆), and d(A₂₀)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. When going from d(A₄) to d(A₁₆), the strand break cross section increases with oligonucleotide length, but only at 7.0 and 8.4 eV, i.e., close to the maximum of the negative ion resonance, the increase in the strand break cross section with the length is similar to the increase of an estimated geometrical cross section. For d(A₂₀), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA₂₀ sequence. The results indicate that, although there is a general length dependence of strand break cross sections, individual nucleotides do not contribute independently of the absolute strand break cross section of the whole DNA strand. The absolute quantification of sequence specific strand breaks will help develop a more accurate molecular level understanding of radiation induced DNA damage, which can then be used for optimized risk estimates in cancer radiation therapy. KW - DNA origami KW - DNA radiation damage KW - DNA strand breaks KW - low-energy electrons KW - sequence dependence Y1 - 2019 U6 - https://doi.org/10.3390/ijms21010111 SN - 1422-0067 VL - 21 IS - 1 PB - Molecular Diversity Preservation International CY - Basel ER -