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Status: Bibliographieeintrag

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Verfasst von:Scherthan, Harry [VerfasserIn]   i
 Chojowski, Robert [VerfasserIn]   i
 Hausmann, Michael [VerfasserIn]   i
Titel:Nanostructure of clustered DNA damage in leukocytes after in-solution irradiation with the alpha emitter Ra-223
Verf.angabe:Harry Scherthan, Jin-Ho Lee, Emanuel Maus, Sarah Schumann, Razan Muhtadi, Robert Chojowski, Matthias Port, Michael Lassmann, Felix Bestvater and Michael Hausmann
E-Jahr:2019
Jahr:26 November 2019
Umfang:23 S.
Fussnoten:Gesehen am 18.02.2020
Titel Quelle:Enthalten in: Cancers
Ort Quelle:Basel : MDPI, 2009
Jahr Quelle:2019
Band/Heft Quelle:11(2019,12) Artikel-Nummer 1877, 23 Seiten
ISSN Quelle:2072-6694
Abstract:Background: Cancer patients are increasingly treated with alpha-particle-emitting radiopharmaceuticals. At the subcellular level, alpha particles induce densely spaced ionizations and molecular damage. Induction of DNA lesions, especially clustered DNA double-strand breaks (DSBs), threatens a cell’s survival. Currently, it is under debate to what extent the spatial topology of the damaged chromatin regions and the repair protein arrangements are contributing. Methods: Super-resolution light microscopy (SMLM) in combination with cluster analysis of single molecule signal-point density regions of DSB repair markers was applied to investigate the nano-structure of DNA damage foci tracks of Ra-223 in-solution irradiated leukocytes. Results: Alpha-damaged chromatin tracks were efficiently outlined by γ-H2AX that formed large (super) foci composed of numerous 60–80 nm-sized nano-foci. Alpha damage tracks contained 60–70% of all γ-H2AX point signals in a nucleus, while less than 30% of 53BP1, MRE11 or p-ATM signals were located inside γ-H2AX damage tracks. MRE11 and p-ATM protein fluorescent tags formed focal nano-clusters of about 20 nm peak size. There were, on average, 12 (±9) MRE11 nanoclusters in a typical γ-H2AX-marked alpha track, suggesting a minimal number of MRE11-processed DSBs per track. Our SMLM data suggest regularly arranged nano-structures during DNA repair in the damaged chromatin domain.
DOI:doi:10.3390/cancers11121877
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.3390/cancers11121877
 Verlag: https://www.mdpi.com/2072-6694/11/12/1877
 DOI: https://doi.org/10.3390/cancers11121877
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:complex DNA damage
 DNA repair
 DSB focus substructure
 high LET irradiation
 Single Molecule Localization Microscopy (SMLM)
K10plus-PPN:1690253126
Verknüpfungen:→ Zeitschrift

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