Averbek, Sera ; Jakob, Burkhard ; Durante, Marco ; Averbeck, Nicole B. (2024)
O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair.
In: International Journal of Molecular Sciences, 2021, 22 (11)
doi: 10.26083/tuprints-00022299
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Exposing cells to DNA damaging agents, such as ionizing radiation (IR) or cytotoxic chemicals, can cause DNA double-strand breaks (DSBs), which are crucial to repair to maintain genetic integrity. O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification (PTM), which has been reported to be involved in the DNA damage response (DDR) and chromatin remodeling. Here, we investigated the impact of O-GlcNAcylation on the DDR, DSB repair and chromatin status in more detail. We also applied charged particle irradiation to analyze differences of O-GlcNAcylation and its impact on DSB repair in respect of spatial dose deposition and radiation quality. Various techniques were used, such as the γH2AX foci assay, live cell microscopy and Fluorescence Lifetime Microscopy (FLIM) to detect DSB rejoining, protein accumulation and chromatin states after treating the cells with O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) inhibitors. We confirmed that O-GlcNAcylation of MDC1 is increased upon irradiation and identified additional repair factors related to Homologous Recombination (HR), CtIP and BRCA1, which were increasingly O-GlcNAcyated upon irradiation. This is consistent with our findings that the function of HR is affected by OGT inhibition. Besides, we found that OGT and OGA activity modulate chromatin compaction states, providing a potential additional level of DNA-repair regulation.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Averbek, Sera ; Jakob, Burkhard ; Durante, Marco ; Averbeck, Nicole B. |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair |
| Sprache: | Englisch |
| Publikationsjahr: | 12 Januar 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2021 |
| Ort der Erstveröffentlichung: | Basel |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | International Journal of Molecular Sciences |
| Jahrgang/Volume einer Zeitschrift: | 22 |
| (Heft-)Nummer: | 11 |
| Kollation: | 20 Seiten |
| DOI: | 10.26083/tuprints-00022299 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/22299 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Exposing cells to DNA damaging agents, such as ionizing radiation (IR) or cytotoxic chemicals, can cause DNA double-strand breaks (DSBs), which are crucial to repair to maintain genetic integrity. O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification (PTM), which has been reported to be involved in the DNA damage response (DDR) and chromatin remodeling. Here, we investigated the impact of O-GlcNAcylation on the DDR, DSB repair and chromatin status in more detail. We also applied charged particle irradiation to analyze differences of O-GlcNAcylation and its impact on DSB repair in respect of spatial dose deposition and radiation quality. Various techniques were used, such as the γH2AX foci assay, live cell microscopy and Fluorescence Lifetime Microscopy (FLIM) to detect DSB rejoining, protein accumulation and chromatin states after treating the cells with O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) inhibitors. We confirmed that O-GlcNAcylation of MDC1 is increased upon irradiation and identified additional repair factors related to Homologous Recombination (HR), CtIP and BRCA1, which were increasingly O-GlcNAcyated upon irradiation. This is consistent with our findings that the function of HR is affected by OGT inhibition. Besides, we found that OGT and OGA activity modulate chromatin compaction states, providing a potential additional level of DNA-repair regulation. |
| Freie Schlagworte: | O-GlcNAcylation, DNA-DSB repair, chromatin remodeling, high LET, particle irradiation, ionizing radiation |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-222999 |
| Zusätzliche Informationen: | This article belongs to the Special Issue Molecular Mechanisms Safeguarding Genome Integrity in DNA Replication, Repair and Transcription |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 530 Physik 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair 05 Fachbereich Physik 05 Fachbereich Physik > Institut für Physik Kondensierter Materie (IPKM) |
| Hinterlegungsdatum: | 12 Jan 2024 13:38 |
| Letzte Änderung: | 15 Jan 2024 08:09 |
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| Suche nach Titel in: | TUfind oder in Google |
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