@misc{LeeBobkovaGieretal.2019, author = {Lee, Jin-Ho and Bobkova, Elizaveta and Gier, Theresa and Gote, Martin and Schmidt-kaler, Fanz and Brieger, Emily and Maus, Emanuel and Krufczik, Matthias and Chojowski, Robert and Korn, Friederike and Sarah, Schumann and Scherthan, Harry and Falkova, Iva and Falk, Martin and Hausmann, Michael and Hildenbrand, Georg}, title = {Mechanisms and Challenges for Understanding Radiation Induced Changes in Chromatin Nanoarchitecture}, series = {DRO 2018}, journal = {DRO 2018}, doi = {https://doi.org/10.13140/RG.2.2.31391.20647}, year = {2019}, abstract = {The three-dimensional architecture of genomes acts as an additional level of mode for fundamental biological processes such as DNA damage response. In this context, nanoprobing and super-resolution microscopy are powerful methods for structural analyses of genomic targets in native chromatin of single cells at resolutions of single antibodies, proteins, histones, short DNA stretches, etc. We used multi-color chromatin nanoprobing and single molecule localization microscopy of established DNA damage and chromatin markers in 3D-conserved nuclei of different cell types exposed to various types and doses of ionizing radiation. Similarly, effect of gold nanoparticles on extent and direction of cellular radiation response was assessed. Our studies revealed the nanoarchitecture of damage foci with respect to γH2AX, Mre11 or 53BP1 and their molecular rearrangements during repair processes. Nanoscopy of genomic Alu resulted in linear-quadratic dose-effects for low to higher dose ranges and in changes of H3K9me3 distribution around Alu clusters upon radiation exposure. Preliminary results show post-irradiation time dependent changes in Alu chromatin. Moreover, gold nanoparticles incorporated into cells seem to act by an interplay of radiation enhancement and chromatin remodeling leading to altered radiosensitivity. Our results contribute to the understanding of cellular radiation responses, thereby laying the basis for improved biological dosimetry and radiotherapies in future.}, subject = {Genom}, language = {en} }