Please use this identifier to cite or link to this item:
doi:10.22028/D291-35303
Title: | Nuclear Fragility in Radiation-Induced Senescence: Blebs and Tubes Visualized by 3D Electron Microscopy |
Author(s): | Freyter, Benjamin M. Abd Al-razaq, Mutaz A. Isermann, Anna Dietz, Anne Azimzadeh, Omid Hekking, Liesbeth Gomolka, Maria Rübe, Claudia E. |
Language: | English |
Title: | Cells |
Volume: | 11 |
Issue: | 2 |
Publisher/Platform: | MDPI |
Year of Publication: | 2022 |
Free key words: | cellular senescence ionizing radiation radiation-induced senescence chromatin reorganization nuclear blebbing transmission electron microscopy (TEM) serial block-face scanning electron microscopy (SBF-SEM) cytosolic chromatin fragments (CCF) cGAS-STING signaling |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | Irreparable DNA damage following ionizing radiation (IR) triggers prolonged DNA dam age response and induces premature senescence. Cellular senescence is a permanent state of cell-cycle arrest characterized by chromatin restructuring, altered nuclear morphology and acquisition of secretory phenotype, which contributes to senescence-related inflammation. However, the mech anistic connections for radiation-induced DNA damage that trigger these senescence-associated hallmarks are poorly understood. In our in vitro model of radiation-induced senescence, mass spectrometry-based proteomics was combined with high-resolution imaging techniques to investi gate the interrelations between altered chromatin compaction, nuclear envelope destabilization and nucleo-cytoplasmic chromatin blebbing. Our findings confirm the general pathophysiology of the senescence-response, with disruption of nuclear lamin organization leading to extensive chromatin restructuring and destabilization of the nuclear membrane with release of chromatin fragments into the cytosol, thereby activating cGAS-STING-dependent interferon signaling. By serial block-face scanning electron microscopy (SBF-SEM) whole-cell datasets were acquired to investigate the mor phological organization of senescent fibroblasts. High-resolution 3-dimensional (3D) reconstruction of the complex nuclear shape allows us to precisely visualize the segregation of nuclear blebs from the main nucleus and their fusion with lysosomes. By multi-view 3D electron microscopy, we identified nanotubular channels formed in lamin-perturbed nuclei of senescent fibroblasts; the potential role of these nucleo-cytoplasmic nanotubes for expulsion of damaged chromatin has to be examined. |
DOI of the first publication: | 10.3390/cells11020273 |
Link to this record: | urn:nbn:de:bsz:291--ds-353033 hdl:20.500.11880/32251 http://dx.doi.org/10.22028/D291-35303 |
ISSN: | 2073-4409 |
Date of registration: | 27-Jan-2022 |
Description of the related object: | Supplementary Materials |
Related object: | https://www.mdpi.com/article/10.3390/cells11020273/s1 |
Faculty: | M - Medizinische Fakultät |
Department: | M - Radiologie |
Professorship: | M - Prof. Dr. Christian Rübe |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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cells-11-00273-v2.pdf | 7,02 MB | Adobe PDF | View/Open |
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