dc.creator | Martínez Macías, María Isabel | es |
dc.creator | Green, Ryan L. | es |
dc.creator | Gómez Herreros, Fernando | es |
dc.creator | Naumann, Marcel | es |
dc.creator | Hermann, Andreas | es |
dc.creator | Hafezparast, Majid | es |
dc.creator | Caldecott, Keith W. | es |
dc.creator | Moore, Duncan A. Q. | es |
dc.creator | Damme, Philip Van | es |
dc.date.accessioned | 2019-07-09T11:07:34Z | |
dc.date.available | 2019-07-09T11:07:34Z | |
dc.date.issued | 2019-02-26 | |
dc.identifier.citation | 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. | |
dc.identifier.issn | 2575-1077 | es |
dc.identifier.uri | https://hdl.handle.net/11441/87960 | |
dc.description.abstract | 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 | es |
dc.description.sponsorship | Helmholtz Virtual Institute VH-VI-510 | es |
dc.description.sponsorship | MRC MR/K01854X/1 SIDSCA 694996 MR/P010121/1 | es |
dc.description.sponsorship | ERC SIDSCA 694996 MR/P010121/1 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Rockefeller University Press | es |
dc.relation.ispartof | Life Science Alliance, 2 (2), e201800222-1-e201800222-14. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Instituto de Biomedicina de Sevilla (IBIS) | es |
dc.relation.projectID | VH-VI-510 | es |
dc.relation.projectID | MR/P010121/1 | es |
dc.relation.projectID | SIDSCA 694996 | es |
dc.relation.projectID | MR/K01854X/1 | es |
dc.relation.publisherversion | http://doi.org/10.26508/lsa.201800222 | es |
dc.identifier.doi | 10.26508/lsa.201800222 | es |
idus.format.extent | 14 p. | es |
dc.journaltitle | Life Science Alliance | es |
dc.publication.volumen | 2 | es |
dc.publication.issue | 2 | es |
dc.publication.initialPage | e201800222-1 | es |
dc.publication.endPage | e201800222-14 | es |