Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA

Abstract

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(A 4 ), d(A 8 ), d(A 12 ), d(A 16 ), and d(A 20 )) 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(A 4 ) to d(A 16 ), 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(A 20 ), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA 20 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.

Monte Carlo Simulation of SARS-CoV-2 Radiation-Induced Inactivation for Vaccine Development

“…Studies published in the literature on DNA damage reported breaks induced by low-energy electrons. The incident energies ranged between 1 eV and 30 eV (38)(39)(40)(41), and damage was induced by energies as low as 3-5 eV. Taking these values into account we determined that an energy deposition above a threshold of 10 eV, positioned on the RNA volume, is considered a damage.…”

Low-Energy Electron Damage to Plasmid DNA in Thin Films: Dependence on Substrates, Surface Density, Charging, Environment, and Uniformity

“…During the last two decades, our knowledge of the interaction of low-energy (0–20 eV) electrons (LEEs) with DNA has been derived from experiments performed with various types of targets ranging from fundamental units (i.e., the bases, sugar, and phosphate groups), − oligonucleotides , to plasmid DNA, − which is composed of thousands of base pairs. The results were obtained from different types of LEE-impact experiments on gaseous molecules, such as the bases, − deoxyribose-ring analogs, , phosphate model compounds, nucleosides, monophosphate nucleosides, and such molecules embedded in water clusters − or as binary H 2 O-biomolecule targets. , Experiments in water were performed with electrons generated by laser beams , and pulse radiolysis. − Many LEE-impact experiments were performed in vacuum on thin films of oligonucleotides attached to an origami template. − Because LEEs account for the major portion of the secondary electron (SE) distribution produced by ionizing radiation, research in this field has contributed in many ways to our present comprehension of the mechanisms of radiobiological damage and their applications, − including the sensitization of radiotherapy − and phototherapy. ,− During about the same length of time, comprehensive theoretical descriptions of the interactions between DNA and LEEs have emerged in the literature. ,− …”

Low-Energy (5–20 eV) Electron-Induced Single and Double Strand Breaks in Well-Defined DNA Sequences

“…Compared to other experimental approaches, the advantage of the DNA origami technique is the relatively simple absolute quantification of strand break yields, the versatility in the choice of target sequences, and the possibility to irradiate two sequences in a single irradiation experiment providing a perfect comparison of the response of two target sequences. In previous work, absolute single strand break cross sections have been determined for homooligomers, , mixed sequences, telomeric DNA, and ssDNA sensitized with potential radiosensitizers. − In addition to LEE irradiation, also experiments with vacuum-UV radiation as well as X-rays and γ rays have been performed. However, so far only single strand break cross sections have been determined.…”

“…An absolute cross section for DNA SBs can be determined from the slope of the exposure−response curves (Figure 2). been determined for homooligomers, 20,21 mixed sequences, 22 telomeric DNA, 23 and ssDNA sensitized with potential radiosensitizers. 24−26 In addition to LEE irradiation, also experiments with vacuum-UV radiation 21 as well as X-rays and γ rays 27 have been performed.…”