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dc.creatorMartínez Macías, María Isabeles
dc.creatorGreen, Ryan L.es
dc.creatorGómez Herreros, Fernandoes
dc.creatorNaumann, Marceles
dc.creatorHermann, Andreases
dc.creatorHafezparast, Majides
dc.creatorCaldecott, Keith W.es
dc.creatorMoore, Duncan A. Q.es
dc.creatorDamme, Philip Vanes
dc.date.accessioned2019-07-09T11:07:34Z
dc.date.available2019-07-09T11:07:34Z
dc.date.issued2019-02-26
dc.identifier.citationMartínez 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.issn2575-1077es
dc.identifier.urihttps://hdl.handle.net/11441/87960
dc.description.abstractFUS (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 neurodegenerationes
dc.description.sponsorshipHelmholtz Virtual Institute VH-VI-510es
dc.description.sponsorshipMRC MR/K01854X/1 SIDSCA 694996 MR/P010121/1es
dc.description.sponsorshipERC SIDSCA 694996 MR/P010121/1es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherRockefeller University Presses
dc.relation.ispartofLife Science Alliance, 2 (2), e201800222-1-e201800222-14.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleFUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stresses
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationInstituto de Biomedicina de Sevilla (IBIS)es
dc.relation.projectIDVH-VI-510es
dc.relation.projectIDMR/P010121/1es
dc.relation.projectIDSIDSCA 694996es
dc.relation.projectIDMR/K01854X/1es
dc.relation.publisherversionhttp://doi.org/10.26508/lsa.201800222es
dc.identifier.doi10.26508/lsa.201800222es
idus.format.extent14 p.es
dc.journaltitleLife Science Alliancees
dc.publication.volumen2es
dc.publication.issue2es
dc.publication.initialPagee201800222-1es
dc.publication.endPagee201800222-14es

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as: Attribution-NonCommercial-NoDerivatives 4.0 Internacional