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Article

O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair

1
Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung GmbH, 64291 Darmstadt, Germany
2
Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany
3
Department of Physics, Technische Universität Darmstadt, 64287 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Ennio Prosperi and Ornella Cazzalini
Int. J. Mol. Sci. 2021, 22(11), 5715; https://doi.org/10.3390/ijms22115715
Received: 3 May 2021 / Revised: 20 May 2021 / Accepted: 21 May 2021 / Published: 27 May 2021
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. View Full-Text
Keywords: O-GlcNAcylation; DNA-DSB repair; chromatin remodeling; high LET; particle irradiation; ionizing radiation O-GlcNAcylation; DNA-DSB repair; chromatin remodeling; high LET; particle irradiation; ionizing radiation
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MDPI and ACS Style

Averbek, S.; Jakob, B.; Durante, M.; Averbeck, N.B. O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair. Int. J. Mol. Sci. 2021, 22, 5715. https://doi.org/10.3390/ijms22115715

AMA Style

Averbek S, Jakob B, Durante M, Averbeck NB. O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair. International Journal of Molecular Sciences. 2021; 22(11):5715. https://doi.org/10.3390/ijms22115715

Chicago/Turabian Style

Averbek, Sera; Jakob, Burkhard; Durante, Marco; Averbeck, Nicole B. 2021. "O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair" Int. J. Mol. Sci. 22, no. 11: 5715. https://doi.org/10.3390/ijms22115715

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