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dc.creatorSalas Armenteros, Irenees
dc.creatorBarroso Ceballos, Sonia Inéses
dc.creatorGarcía Rondón, Anaes
dc.creatorPérez Calero, Mónicaes
dc.creatorAndújar, Eloísaes
dc.creatorLuna Varo, Rosa Maríaes
dc.creatorAguilera López, Andrés
dc.date.accessioned2019-09-09T11:24:11Z
dc.date.available2019-09-09T11:24:11Z
dc.date.issued2019
dc.identifier.citationSalas Armenteros, I., Barroso Ceballos, S.I., García Rondón, A., Pérez Calero, M., Andújar, E., Luna Varo, R.M. y Aguilera López, A. (2019). Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability. Cell Reports, 28 (6), 1551-1563.
dc.identifier.issn2211-1247es
dc.identifier.urihttps://hdl.handle.net/11441/89062
dc.description.abstractTHO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein 1), a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs cell proliferation and genome integrity, increasing γH2AX foci and DNA breaks. This phenotype is not dependent on either transcription or RNA-DNA hybrids. Mutations in the yeast orthologous gene SPP381 cause similar transcription-independent genome instability, supporting a conserved role. MFAP1 depletion has a wide effect on splicing and gene expression in human cells, determined by transcriptome analyses. MFAP1 depletion affects a number of DNA damage response (DDR) genes, which supports an indirect role of MFAP1 on genome integrity. Our work defines a functional interaction between THO and RNA processing and argues that splicing factors may contribute to genome integrity indirectly by regulating the expression of DDR genes rather than by a direct role.es
dc.description.sponsorshipEuropean ResearchCouncil (grant ERC2014 AdG669898 TARLOOP)es
dc.description.sponsorshipJunta de Andalucía Spain (grant BIO1238)es
dc.description.sponsorshipSpanish Ministry of Economy and Competitiveness (grant BFU2016-75058-P)es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherElsevieres
dc.relation.ispartofCell Reports, 28 (6), 1551-1563.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectTHO complexes
dc.subjectalernative splicinges
dc.subjectMFAP1/SPP381es
dc.subjectgenome instabilityes
dc.titleDepletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instabilityes
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.affiliationUniversidad de Sevilla. Departamento de Genéticaes
dc.relation.projectIDERC2014 AdG669898 TARLOOPes
dc.relation.projectIDgrant BFU2016-75058-Pes
dc.relation.projectIDgrant BIO1238es
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.celrep.2019.07.010es
dc.identifier.doi10.1016/j.celrep.2019.07.010es
idus.format.extent12 p.es
dc.journaltitleCell Reportses
dc.publication.volumen28es
dc.publication.issue6es
dc.publication.initialPage1551es
dc.publication.endPage1563es

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