TY  - JOUR
A1  - Trifault, Barbara
A1  - Mamontova, Victoria
A1  - Cossa, Giacomo
A1  - Ganskih, Sabina
A1  - Wei, Yuanjie
A1  - Hofstetter, Julia
A1  - Bhandare, Pranjali
A1  - Baluapuri, Apoorva
A1  - Nieto, Blanca
A1  - Solvie, Daniel
A1  - Ade, Carsten P.
A1  - Gallant, Peter
A1  - Wolf, Elmar
A1  - Larsen, Dorthe H.
A1  - Munschauer, Mathias
A1  - Burger, Kaspar
T1  - Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts
JF  - Nucleic Acids Research
N2  - 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-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.
KW  - genome integrity
KW  - repair and replication
KW  - NONO
KW  - DNA double-strand breaks
KW  - aberrant transcripts
Y1  - 2024
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350208
VL  - 52
IS  - 6
ER  -