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 - JOUR A1 - Vogel, Stefanie A1 - Ebel, Kenny A1 - Heck, Christian A1 - Schürmann, Robin Mathis A1 - Milosavljevic, Aleksandar R. A1 - Giuliani, Alexandre A1 - Bald, Ilko T1 - Vacuum-UV induced DNA strand breaks BT - influence of the radiosensitizers 5-bromouracil and 8-bromoadenine JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1039/c8cp06813e SN - 1463-9076 SN - 1463-9084 VL - 21 IS - 4 SP - 1972 EP - 1979 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Schleger, C. A1 - Heck, R. A1 - Steinberg, Pablo T1 - The role of wild-type and mutated N-ras in the malignant transformation of liver cells Y1 - 2000 ER - TY - BOOK A1 - Ackermann, Peter A1 - Ahlgrimm, Frederik A1 - Apelojg, Benjamin A1 - Börnert-Ringleb, Moritz A1 - Borowski, Andreas A1 - Ehlert, Antje A1 - Eichler, Constanze A1 - Frohn, Julia A1 - Gehrmann, Marie-Luise A1 - Gerlach, Erin A1 - Goetz, Ilka A1 - Goral, Johanna A1 - Gronostaj, Anna A1 - Grubert, Jana A1 - Güleryüz, Burak A1 - Hacke, Alexander A1 - Heck, Sebastian A1 - Hermanns, Jolanda A1 - Hochmuth, Jörg A1 - Jennek, Julia A1 - Jostes, Brigitte A1 - Jurczok, Anne A1 - Kleemann, Katrin A1 - Kortenkamp, Ulrich A1 - Krauskopf, Karsten A1 - Kücholl, Denise A1 - Kulawiak, Pawel R. A1 - Lauterbach, Wolfgang A1 - Lazarides, Rebecca A1 - Linka, Tim A1 - Löweke, Sebastian A1 - Lohse-Bossenz, Hendrik A1 - Maar, Verena A1 - Nowak, Anna A1 - Ratzlaff, Olaf A1 - Reitz-Koncebovski, Karen A1 - Rother, Stefanie A1 - Scherreiks, Lynn A1 - Schroeder, Christoph A1 - Schwalbe, Anja A1 - Schwill, Andreas A1 - Tosch, Frank A1 - Vock, Miriam A1 - Wagner, Luisa A1 - Westphal, Andrea A1 - Wilbert, Jürgen ED - Borowski, Andreas ED - Ehlert, Antje ED - Prechtl, Helmut T1 - PSI-Potsdam BT - Ergebnisbericht zu den Aktivitäten im Rahmen der Qualitätsoffensive Lehrerbildung (2015-2018) T3 - Potsdamer Beiträge zur Lehrerbildung und Bildungsforschung N2 - 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. T3 - Potsdamer Beiträge zur Lehrkräftebildung und Bildungsforschung - 1 KW - Lehrerbildung KW - Innovative Lehrkonzepte KW - Vernetzungen KW - Erhebungsinstrumente KW - Praxisphasen Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-414542 SN - 978-3-86956-442-5 SN - 2626-3556 SN - 2626-4722 IS - 1 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Galhuber, Markus A1 - Michenthaler, Helene A1 - Heininger, Christoph A1 - Reinisch, Isabel A1 - Nössing, Christoph A1 - Krstic, Jelena A1 - Kupper, Nadja A1 - Moyschewitz, Elisabeth A1 - Auer, Martina A1 - Heitzer, Ellen A1 - Ulz, Peter A1 - Birner-Gruenberger, Ruth A1 - Liesinger, Laura A1 - Lenihan-Geels, Georgia Ngawai A1 - Oster, Moritz A1 - Spreitzer, Emil A1 - Chiozzi, Riccardo Zenezini A1 - Schulz, Tim J. A1 - Schupp, Michael A1 - Madl, Tobias A1 - Heck, Albert J. R. A1 - Prokesch, Andreas T1 - Complementary omics strategies to dissect p53 signaling networks under nutrient stress JF - Cellular and molecular life sciences N2 - 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. KW - p53 signaling KW - Nutrient stress KW - Starvation KW - Interactome KW - p53 targets Y1 - 2022 U6 - https://doi.org/10.1007/s00018-022-04345-8 SN - 1420-682X SN - 1420-9071 VL - 79 IS - 6 PB - Springer Nature CY - Basel ER -