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Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-350208
- RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54\(^{nrb}\) marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-codingRNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54\(^{nrb}\) marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA–RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.…
Autor(en): | Barbara TrifaultORCiD, Victoria Mamontova, Giacomo Cossa, Sabina Ganskih, Yuanjie Wei, Julia Hofstetter, Pranjali Bhandare, Apoorva BaluapuriORCiD, Blanca Nieto, Daniel Solvie, Carsten P. Ade, Peter Gallant, Elmar Wolf, Dorthe H. Larsen, Mathias Munschauer, Kaspar BurgerORCiD |
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URN: | urn:nbn:de:bvb:20-opus-350208 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Klinische Biochemie und Pathobiochemie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Nucleic Acids Research |
Erscheinungsjahr: | 2024 |
Band / Jahrgang: | 52 |
Heft / Ausgabe: | 6 |
Seitenangabe: | 3050-3068 |
Originalveröffentlichung / Quelle: | Nucleic Acids Research (2024) 52:6, 3050-3068. DOI: 10.1093/nar/gkae022 |
DOI: | https://doi.org/10.1093/nar/gkae022 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | DNA double-strand breaks; NONO; aberrant transcripts; genome integrity; repair and replication |
Datum der Freischaltung: | 16.04.2024 |
EU-Projektnummer / Contract (GA) number: | 759139 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |