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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.
Radiation therapy is a basic part of cancer treatment. To increase the DNA damage in carcinogenic cells and preserve healthy tissue at the same time, radiosensitizing molecules such as halogenated nucleobase analogs can be incorporated into the DNA during the cell reproduction cycle. In the present study 8.44 eV photon irradiation induced single strand breaks (SSB) in DNA sequences modified with the radiosensitizer 5-bromouracil (U-5Br) and 8-bromoadenine ((8Br)A) are investigated. U-5Br was incorporated in the 13mer oligonucleotide flanked by different nucleobases. It was demonstrated that the highest SSB cross sections were reached, when cytosine and thymine were adjacent to U-5Br, whereas guanine as a neighboring nucleobase decreases the activity of U-5Br indicating that competing reaction mechanisms are active. This was further investigated with respect to the distance of guanine to U-5Br separated by an increasing number of adenine nucleotides. It was observed that the SSB cross sections were decreasing with an increasing number of adenine spacers between guanine and U-5Br until the SSB cross sections almost reached the level of a non-modified DNA sequence, which demonstrates the high sequence dependence of the sensitizing effect of U-5Br. (8Br)A was incorporated in a 13mer oligonucleotide as well and the strand breaks were quantified upon 8.44 eV photon irradiation in direct comparison to a non-modified DNA sequence of the same composition. No clear enhancement of the SSB yield of the modified in comparison to the non-modified DNA sequence could be observed. Additionally, secondary electrons with a maximum energy of 3.6 eV were generated when using Si as a substrate giving rise to further DNA damage. A clear enhancement in the SSB yield can be ascertained, but to the same degree for both the non-modified DNA sequence and the DNA sequence modified with (8Br)A.
PSI-Potsdam
(2018)
In Brandenburg kommt der Universität Potsdam eine besondere Rolle zu: Sie ist die einzige, an der zukünftige Lehrerinnen und Lehrer die erste Phase ihres Werdegangs – das Lehramtsstudium – absolvieren können. Vor diesem Hintergrund wurde bereits kurz nach der Gründung im Jahr 1991 das „Potsdamer Modell der Lehrerbildung“ entwickelt. Dieses Modell strebt fortlaufend eine enge Verzahnung von Theorie und Praxis über das gesamte Studium hinweg an und bindet hierfür die schulpraktischen Studienanteile in besonderer Weise ein. Eine erneute Stärkung erfuhr die Lehrerbildung im Dezember 2014 mit der Gründung des Zentrums für Lehrerbildung und Bildungsforschung (ZeLB). Aus der koordinierenden Arbeit des Zentrums entstand das fakultätsübergreifende Projekt „Professionalisierung – Schulpraktische Studien – Inklusion“ (PSI-Potsdam) das im Rahmen der Qualitätsoffensive Lehrerbildung des Bundesministeriums für Bildung und Forschung erfolgreich gefördert wurde (2015–2018) und dessen Verlängerung (2019–2023) bewilligt ist.
Der vorliegende Band vermittelt in den drei großen Kapiteln „Erhebungsinstrumente“, „Seminarkonzepte“ und „Vernetzungen“ einen Überblick über einige der praxisnahen Forschungszugänge, hochschuldidaktischen Ansätze und Strategien zur Vernetzung innerhalb der Lehrerbildung, die im Rahmen von PSI-Potsdam entwickelt und umgesetzt wurden. Die Beiträge wurden mit dem Ziel verfasst, Kolleginnen und Kollegen an Universitäten und Hochschulen, Akteur_innen des Vorbereitungsdiensts sowie der Fort- und Weiterbildung von Lehrkräften möglichst konkrete Einblicke zu gewähren.
Unter der Herausgeberschaft von Prof. Dr. Andreas Borowski (Fachdidaktik Physik), Prof. Dr. Antje Ehlert (Inklusionspädagogik mit dem Förderschwerpunkt Lernen) und Prof. Dr. Helmut Prechtl (Fachdidaktik Biologie) vereinen sich Autor_innen mit breit gestreuter fachdidaktischer und bildungswissenschaftlicher Expertise.
Signaling trough p53is a major cellular stress response mechanism and increases upon nutrient stresses such as starvation. Here, we show in a human hepatoma cell line that starvation leads to robust nuclear p53 stabilization. Using BioID, we determine the cytoplasmic p53 interaction network within the immediate-early starvation response and show that p53 is dissociated from several metabolic enzymes and the kinase PAK2 for which direct binding with the p53 DNA-binding domain was confirmed with NMR studies. Furthermore, proteomics after p53 immunoprecipitation (RIME) uncovered the nuclear interactome under prolonged starvation, where we confirmed the novel p53 interactors SORBS1 (insulin receptor signaling) and UGP2 (glycogen synthesis). Finally, transcriptomics after p53 re-expression revealed a distinct starvation-specific transcriptome response and suggested previously unknown nutrient-dependent p53 target genes. Together, our complementary approaches delineate several nodes of the p53 signaling cascade upon starvation, shedding new light on the mechanisms of p53 as nutrient stress sensor. Given the central role of p53 in cancer biology and the beneficial effects of fasting in cancer treatment, the identified interaction partners and networks could pinpoint novel pharmacologic targets to fine-tune p53 activity.