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| Status |
Public on Jan 16, 2024 |
| Title |
Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts [BLISS] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localisation to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localisation is poorly understood. Here we show that the topoisomerase-II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-induced nucleolar antisense RNAs (diNARs) in human cancer cells. diNARs originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in ab RRM1 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 signaling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.
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| Overall design |
Profiling of DSBs upon siCTR or siNONO, with or without etoposide treatment
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| Contributor(s) |
Solvie D, Ade CP, Burger K |
| Citation(s) |
38224452 |
| Submission date |
Jul 07, 2023 |
| Last update date |
Apr 16, 2024 |
| Contact name |
Martin Eilers |
| Organization name |
University of Wuerzburg
|
| Department |
Chair for Biochemistry and Molecular Biology
|
| Lab |
Martin Eilers
|
| Street address |
Am Hubland
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| City |
Wuerzburg |
| ZIP/Postal code |
97074 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE236900 |
Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts |
|
| Relations |
| BioProject |
PRJNA992562 |
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