TY - JOUR A1 - Hausmann, Michael A1 - Neitzel, Charlotte A1 - Bobkova, Elizaveta A1 - Nagel, David A1 - Hofmann, Andreas A1 - Chramko, Tatyana A1 - Smirnova, Elena A1 - Kopecna, Olga A1 - Pagáčová, Eva A1 - Boreyko, Alla A1 - Krasavin, Evgeny A1 - Falkova, Iva A1 - Heermann, Dieter W. A1 - Pilarczyk, Götz A1 - Hildenbrand, Georg A1 - Bestvater, Felix A1 - Falk, Martin T1 - Single Molecule Localization Microscopy Analyses of DNA-Repair Foci and Clusters Detected Along Particle Damage Tracks JF - Frontiers in Physics KW - Krebszelle KW - Strahlentherapie KW - Genom KW - Zellkern Y1 - 2020 U6 - https://doi.org/https://doi.org/10.3389/fphy.2020.578662 SN - 2296-424X VL - 8 PB - Frontiers Media SA ER - TY - JOUR A1 - Hausmann, Michael A1 - Falk, Martin A1 - Neitzel, Charlotte A1 - Hofmann, Andreas A1 - Biswas, Abin A1 - Gier, Theresa A1 - Falkova, Iva A1 - Heermann, Dieter W. A1 - Hildenbrand, Georg T1 - Elucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach JF - International Journal of Molecular Sciences N2 - In cancer therapy, the application of (fractionated) harsh radiation treatment is state of the art for many types of tumors. However, ionizing radiation is a “double-edged sword”—it can kill the tumor but can also promote the selection of radioresistant tumor cell clones or even initiate carcinogenesis in the normal irradiated tissue. Individualized radiotherapy would reduce these risks and boost the treatment, but its development requires a deep understanding of DNA damage and repair processes and the corresponding control mechanisms. DNA double strand breaks (DSBs) and their repair play a critical role in the cellular response to radiation. In previous years, it has become apparent that, beyond genetic and epigenetic determinants, the structural aspects of damaged chromatin (i.e., not only of DSBs themselves but also of the whole damage-surrounding chromatin domains) form another layer of complex DSB regulation. In the present article, we summarize the application of super-resolution single molecule localization microscopy (SMLM) for investigations of these structural aspects with emphasis on the relationship between the nano-architecture of radiation-induced repair foci (IRIFs), represented here by γH2AX foci, and their chromatin environment. Using irradiated HeLa cell cultures as an example, we show repair-dependent rearrangements of damaged chromatin and analyze the architecture of γH2AX repair clusters according to topological similarities. Although HeLa cells are known to have highly aberrant genomes, the topological similarity of γH2AX was high, indicating a functional, presumptively genome type-independent relevance of structural aspects in DSB repair. Remarkably, nano-scaled chromatin rearrangements during repair depended both on the chromatin domain type and the treatment. Based on these results, we demonstrate how the nano-architecture and topology of IRIFs and chromatin can be determined, point to the methodological relevance of SMLM, and discuss the consequences of the observed phenomena for the DSB repair network regulation or, for instance, radiation treatment outcomes. KW - Krebszelle KW - Strahlentherapie Y1 - 2021 U6 - https://doi.org/https://doi.org/10.3390/ijms22073636 SN - 1422-0067 VL - 22 IS - 7 PB - MDPI AG ER -