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
ISSN: 2073-4409
Date of registration: 27-Jan-2022
Description of the related object: Supplementary Materials
Related object:
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 SizeFormat 
cells-11-00273-v2.pdf7,02 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons