Počet záznamů: 1  

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

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    SYSNO ASEP0542178
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevElucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach
    Tvůrce(i) Hausmann, M. (DE)
    Falk, Martin (BFU-R) RID, ORCID
    Neitzel, Ch. (DE)
    Hofmann, A. (DE)
    Biswas, A. (DE)
    Gier, T. (DE)
    Falková, Iva (BFU-R) ORCID
    Heermann, D.W. (DE)
    Hildenbrand, G. (DE)
    Celkový počet autorů9
    Číslo článku3636
    Zdroj.dok.International Journal of Molecular Sciences
    Roč. 22, č. 7 (2021)
    Poč.str.25 s.
    Forma vydáníOnline - E
    Jazyk dok.eng - angličtina
    Země vyd.CH - Švýcarsko
    Klíč. slovatopology of DNA double strand breaks ; nano-architecture ; ionizing radiation-induced foci (IRIF) ; chromatin rearrangements after irradiation ; single molecule localization microscopy (SMLM)
    Vědní obor RIVCE - Biochemie
    Obor OECDBiochemistry and molecular biology
    CEPGC20-04109J GA ČR - Grantová agentura ČR
    Způsob publikováníOpen access
    Institucionální podporaBFU-R - RVO:68081707
    UT WOS000638667800001
    EID SCOPUS85103339363
    AnotaceIn 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 gamma H2AX 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 gamma H2AX repair clusters according to topological similarities. Although HeLa cells are known to have highly aberrant genomes, the topological similarity of gamma H2AX 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.
    PracovištěBiofyzikální ústav
    KontaktJana Poláková, polakova@ibp.cz, Tel.: 541 517 244
    Rok sběru2022
    Elektronická adresahttps://www.mdpi.com/1422-0067/22/7/3636
Počet záznamů: 1