Elucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach

  • 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.

Export metadata

Additional Services

Search Google Scholar
Metadaten
Author:Michael HausmannORCiD, Martin FalkORCiD, Charlotte Neitzel, Andreas HofmannORCiD, Abin BiswasORCiD, Theresa Gier, Iva Falkova, Dieter W. HeermannORCiD, Georg HildenbrandORCiD
DOI:https://doi.org/https://doi.org/10.3390/ijms22073636
ISSN:1422-0067
Parent Title (English):International Journal of Molecular Sciences
Publisher:MDPI AG
Document Type:Article
Language:English
Year of Completion:2021
Release Date:2024/11/18
GND Keyword:Krebszelle; Strahlentherapie
Volume:22
Issue:7
Article Number:3636
Institutes:Fakultät Ingenieurwissenschaften und Informatik / Studiengänge / Medical Engineering and Data Science (Bachelor)
research focus :Materials / Material Testing & Sensor Technology
Reviewed:ja
Einverstanden ✔
Diese Webseite verwendet technisch erforderliche Session-Cookies. Durch die weitere Nutzung der Webseite stimmen Sie diesem zu. Unsere Datenschutzerklärung finden Sie hier.