Artículo
FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress
Autor/es | Martínez Macías, María Isabel
Green, Ryan L. Gómez Herreros, Fernando Naumann, Marcel Hermann, Andreas Hafezparast, Majid Caldecott, Keith W. Moore, Duncan A. Q. Damme, Philip Van |
Departamento | Instituto de Biomedicina de Sevilla (IBIS) |
Fecha de publicación | 2019-02-26 |
Fecha de depósito | 2019-07-09 |
Publicado en |
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Resumen | FUS (fused in sarcoma) plays a key role in several steps of RNA metabolism, and dominant mutations in this protein are associated with neurodegenerative diseases. Here, we show that FUS is a component of the cellular ... FUS (fused in sarcoma) plays a key role in several steps of RNA metabolism, and dominant mutations in this protein are associated with neurodegenerative diseases. Here, we show that FUS is a component of the cellular response to topoisomerase I (TOP1)–induced DNA breakage; relocalising to the nucleolus in response to RNA polymerase II (Pol II) stalling at sites of TOP1-induced DNA breaks. This relocalisation is rapid and dynamic, reversing following the removal of TOP1-induced breaks and coinciding with the recovery of global transcription. Importantly, FUS relocalisation following TOP1-induced DNA breakage is associated with increased FUS binding at sites of RNA polymerase I transcription in ribosomal DNA and reduced FUS binding at sites of RNA Pol II transcription, suggesting that FUS relocates from sites of stalled RNA Pol II either to regulate pre-mRNA processing during transcriptional stress or to modulate ribosomal RNA biogenesis. Importantly, FUS-mutant patient fibroblasts are hypersensitive to TOP1-induced DNA breakage, highlighting the possible relevance of these findings to neurodegeneration |
Identificador del proyecto | VH-VI-510
MR/P010121/1 SIDSCA 694996 MR/K01854X/1 |
Cita | Martínez Macías, M.I., Green, R.L., Gómez Herreros, F., Naumann, M., Hermann, A., Hafezparast, M.,...,Damme, P.V. (2019). FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress. Life Science Alliance, 2 (2), e201800222-1-e201800222-14. |
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