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| Verfasst von: | Mancarella, Daniela [VerfasserIn]  |
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| | Ellinghaus, Henrik [VerfasserIn] |
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| | Sigismondo, Gianluca [VerfasserIn] |
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| | Veselinov, Olivera [VerfasserIn] |
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| | Kühn, Alexander [VerfasserIn] |
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| | Goyal, Ashish [VerfasserIn] |
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| | Hartmann, Mark [VerfasserIn] |
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| | Fellenberg, Jörg [VerfasserIn] |
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| | Krijgsveld, Jeroen [VerfasserIn] |
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| | Plass, Christoph [VerfasserIn] |
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| | Popanda, Odilia [VerfasserIn] |
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| | Schmezer, Peter [VerfasserIn] |
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| | Bakr, Ali [VerfasserIn] |
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| Titel: | Deposition of onco-histone H3.3-G34W leads to DNA repair deficiency and activates cGAS/STING-mediated immune responses |
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| Verf.angabe: | Daniela Mancarella, Henrik Ellinghaus, Gianluca Sigismondo, Olivera Veselinov, Alexander Kühn, Ashish Goyal, Mark Hartmann, Jörg Fellenberg, Jeroen Krijgsveld, Christoph Plass, Odilia Popanda, Peter Schmezer, Ali Bakr |
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| E-Jahr: | 2024 |
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| Jahr: | 14 February 2024 |
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| Umfang: | 15 S. |
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| Fussnoten: | Gesehen am 22.07.2024 |
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| Titel Quelle: | Enthalten in: International journal of cancer |
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| Ort Quelle: | Bognor Regis : Wiley-Liss, 1966 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 154(2024), 12, Seite 2106-2120 |
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| ISSN Quelle: | 1097-0215 |
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| Abstract: | Mutations in histone H3.3-encoding genes causing mutant histone tails are associated with specific cancers such as pediatric glioblastomas (H3.3-G34R/V) and giant cell tumor of the bone (H3.3-G34W). The mechanisms by which these mutations promote malignancy are not completely understood. Here we show that cells expressing H3.3-G34W exhibit DNA double-strand breaks (DSBs) repair defects and increased cellular sensitivity to ionizing radiation (IR). Mechanistically, H3.3-G34W can be deposited to damaged chromatin, but in contrast to wild-type H3.3, does not interact with non-homologous end-joining (NHEJ) key effectors KU70/80 and XRCC4 leading to NHEJ deficiency. Together with defective cell cycle checkpoints reported previously, this DNA repair deficiency in H3.3-G34W cells led to accumulation of micronuclei and cytosolic DNA following IR, which subsequently led to activation of the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway, thereby inducing release of immune-stimulatory cytokines. These findings suggest a potential for radiotherapy for tumors expressing H3.3-G34W, which can be further improved by combination with STING agonists to induce immune-mediated therapeutic efficacy. |
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| DOI: | doi:10.1002/ijc.34883 |
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| 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.
kostenfrei: Volltext: https://doi.org/10.1002/ijc.34883 |
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| | kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.34883 |
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| | DOI: https://doi.org/10.1002/ijc.34883 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | cGAS/STING-mediated immune responses |
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| | DNA repair |
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| | H3.3-G34W |
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| | radiation |
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| K10plus-PPN: | 1895988616 |
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| Verknüpfungen: | → Zeitschrift |
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Deposition of onco-histone H3.3-G34W leads to DNA repair deficiency and activates cGAS/STING-mediated immune responses / Mancarella, Daniela [VerfasserIn]; 14 February 2024 (Online-Ressource)
