Anmelden

Open Access

  • Startseite
  • Suchen
  • Browsen
  • Veröffentlichen
  • Hilfe

Filtern

Autor

  • Meyer, Susann (6)
  • Hahn, Marc Benjamin (5)
  • Kunte, Hans-Jörg (4)
  • Solomun, Tihomir (4)
  • Sturm, Heinz (4)
  • Schröter, Maria-Astrid (3)
  • Herrmann, S (1)
  • Kunte, Hans Jörg (1)
  • Kunte, Hans-Joerg (1)
  • Oprzeska-Zingrebe, E. A. (1)
+ weitere

Erscheinungsjahr

  • 2018 (1)
  • 2017 (4)
  • 2015 (1)

Dokumenttyp

  • Zeitschriftenartikel (6) (entfernen)

Schlagworte

  • DNA (3)
  • DNA radiation damage (2)
  • Double-strand break (DSB) (2)
  • Ectoine (2)
  • Lethal dose (2)
  • Low energy electrons (2)
  • Monte Carlo simulation (2)
  • Plasmid DNA in water (2)
  • Radiation damage to biomolecules (2)
  • Single-strand break (SSB) (2)
+ weitere

Organisationseinheit der BAM

  • 4 Material und Umwelt (6) (entfernen)

6 Treffer

  • 1 bis 6
  • CSV
  • RIS
  • 10
  • 20
  • 50
  • 100

Sortieren nach

  • Jahr
  • Jahr
  • Titel
  • Titel
  • Autor
  • Autor
Direct electron irradiation of DNA in fully aqueous environment. Damage determination in combination with Monte Carlo simulations (2017)
Hahn, Marc Benjamin ; Meyer, Susann ; Schröter, Maria-Astrid ; Seitz, H. ; Kunte, Hans-Jörg ; Solomun, Tihomir ; Sturm, Heinz
We report on a study in which plasmid DNA in water was irradiated with 30 keV electrons generated by a scanning electron microscope and passed through a 100 nm thick Si3N4 membrane. The corresponding Monte Carlo simulations suggest that the kinetic energy spectrum of the electrons throughout the water is dominated by low energy electrons (<100 eV). The DNA radiation damage, single-strand breaks (SSB) and double-strand breaks (DSB), was determined by electrophoresis. The median lethal dose of D1/2 = 1.7 ± 0.3 Gy was found to be much smaller compared to partially or fully hydrated DNA irradiated under vacuum conditions. The ratio of DSB to SSB was found to be (1:12) as compared to 1:88) found for hydrated DNA. Our method enables quantitative measurements of radiation damage to biomolecules (DNA, proteins) in solutions under varying conditions (pH, salinity, cosolutes) for an electron energy range which is difficult to probe by standard methods.
Ectoine can enhance structural changes in DNA in vitro (2017)
Meyer, Susann ; Schröter, Maria-Astrid ; Hahn, Marc Benjamin ; Solumon, Tihomir ; Strum, Heinz ; Kunte, Hans Jörg
Strand breaks and conformational changes of DNA have consequences for the physiological role of DNA. The natural protecting molecule ectoine is beneficial to entire bacterial cells and biomolecules such as proteins by mitigating detrimental effects of environmental stresses. It was postulated that ectoine-like molecules bind to negatively charged spheres that mimic DNA surfaces. We investigated the effect of ectoine on DNA and whether ectoine is able to protect DNA from damages caused by ultraviolet radiation (UV-A). In order to determine different isoforms of DNA, agarose gel electrophoresis and atomic force microscopy experiments were carried out with plasmid pUC19 DNA. Our quantitative results revealed that a prolonged incubation of DNA with ectoine leads to an increase in transitions from supercoiled (undamaged) to open circular (single-strand break) conformation at pH 6.6. The effect is pH dependent and no significant changes were observed at physiological pH of 7.5. After UV-A irradiation in ectoine solution, changes in DNA conformation were even more pronounced and this effect was pH dependent. We hypothesize that ectoine is attracted to the negatively charge surface of DNA at lower pH and therefore fails to act as a stabilizing agent for DNA in our in vitro experiments.
Ectoine protects DNA from damage by ionizing radiation (2017)
Schröter, Maria-Astrid ; Meyer, Susann ; Hahn, Marc Benjamin ; Solomun, Tihomir ; Sturm, Heinz ; Kunte, Hans-Jörg
Ectoine plays an important role in protecting biomolecules and entire cells against environmental stressors such as salinity, freezing, drying and high temperatures. Recent studies revealed that ectoine also provides effective protection for human skin cells from damage caused by UV-A radiation. These protective properties make ectoine a valuable compound and it is applied as an active ingredient in numerous pharmaceutical devices and cosmetics. Interestingly, the underlying mechanism resulting in protecting cells from radiation is not yet fully understood. Here we present a study on ectoine and its protective influence on DNA during electron irradiation. Applying gel electrophoresis and atomic force microscopy, we demonstrate for the first time that ectoine prevents DNA strand breaks caused by ionizing electron radiation. The results presented here point to future applications of ectoine for instance in cancer radiation therapy.
Influence of compatible solute ectoine on distinct DNA structures: thermodynamic insights into molecular binding mechanisms and destabilization effects (2018)
Oprzeska-Zingrebe, E. A. ; Meyer, Susann ; Roloff, Alexander ; Kunte, Hans-Jörg ; Smiatek, J.
In nature, the cellular environment of DNA includes not only water and ions, but also other components and co-solutes, which can exert both stabilizing and destabilizing effects on particular oligonucleotide conformations. Among them, ectoine, known as an important osmoprotectant organic co-solute in a broad range of pharmaceutical products, turns out to be of particular relevance. In this article, we study the influence of ectoine on a short single-stranded DNA fragment and on double-stranded helical B-DNA in aqueous solution by means of atomistic molecular dynamics (MD) simulations in combination with molecular theories of solution. Our results demonstrate a conformation-dependent binding behavior of ectoine, which favors the unfolded state of DNA by a combination of electrostatic and dispersion interactions. In conjunction with the Kirkwood–Buff theory, we introduce a simple Framework to compute the influence of ectoine on the DNA melting temperature. Our findings reveal a significant linear decrease of the melting temperature with increasing ectoine concentration, which is found to be in qualitative agreement with results from denaturation experiments. The outcomes of our Computer simulations provide a detailed mechanistic rationale for the surprising destabilizing influence of ectoine on distinct DNA structures.
Influence of the Compatible Solute Ectoine on the Local Water Structure: Implications for the Binding of the Protein G5P to DNA (2015)
Hahn, Marc Benjamin ; Solomun, Tihomir ; Wellhausen, Robert ; Herrmann, S ; Seitz, H ; Meyer, Susann ; Kunte, Hans-Jörg ; Zeman, J. ; Uhlig, F ; Smiatek, J ; Sturm, Heinz
Microorganisms accumulate molar concentrations of compatible solutes like ectoine to prevent proteins from denaturation. Direct structural or spectroscopic information on the mechanism and about the hydration shell around ectoine are scarce. We combined surface plasmon resonance (SPR), confocal Raman spectroscopy, molecular dynamics simulations, and density functional theory (DFT) calculations to study the local hydration shell around ectoine and its influence on the binding of a gene-S-protein (G5P) to a single-stranded DNA (dT(25)). Due to the very high hygroscopicity of ectoine, it was possible to analyze the highly stable hydration shell by confocal Raman spectroscopy. Corresponding molecular dynamics simulation results revealed a significant change of the water dielectric constant in the presence of a high molar ectoine concentration as compared to pure water. The SPR data showed that the amount of protein bound to DNA decreases in the presence of ectoine, and hence, the protein-DNA dissociation constant increases in a concentration-dependent manner. Concomitantly, the Raman spectra in terms of the amide I region revealed large changes in the protein secondary structure. Our results indicate that ectoine strongly affects the molecular recognition between the protein and the oligonudeotide, which has important consequences for osmotic regulation mechanisms.
Measurements and simulations of microscopic damage to DNA in water by 30 keV electrons: A general approach applicable to other radiation sources and biological targets (2017)
Hahn, Marc Benjamin ; Meyer, Susann ; Kunte, Hans-Joerg ; Solomun, Tihomir ; Sturm, Heinz
The determination of the microscopic dose-damage relationship for DNA in an aqueous environment is of a fundamental interest for dosimetry and applications in radiation therapy and protection. We combine geant4 particle-scattering simulations in water with calculations concerning the movement of biomolecules to obtain the energy deposit in the biologically relevant nanoscopic volume. We juxtaposition these results to the experimentally determined damage to obtain the dose-damage relationship at a molecular level. This approach is tested for an experimentally challenging system concerning the direct irradiation of plasmid DNA (pUC19) in water with electrons as primary particles. Here a microscopic target model for the plasmid DNA based on the relation of lineal energy and radiation quality is used to calculate the effective target volume. It was found that on average fewer than two ionizations within a 7.5-nm radius around the sugar-phosphate backbone are sufficient to cause a single strand break, with a corresponding median lethal energy deposit being E1/2=6±4 eV. The presented method is applicable for ionizing radiation (e.g., γ rays, x rays, and electrons) and a variety of targets, such as DNA, proteins, or cells.
  • 1 bis 6

OPUS4 Logo

  • Kontakt
  • Impressum
  • Sitelinks