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dc.creatorGarcía Rubio, María Luisaes
dc.creatorAguilera, Paulaes
dc.creatorLafuente Barquero, Juanes
dc.creatorRuiz, José F.es
dc.creatorSimon, Marie-Noellees
dc.creatorGeli, Vincentes
dc.creatorGarcía Rondón, Anaes
dc.creatorAguilera López, Andréses
dc.date.accessioned2018-08-29T11:57:48Z
dc.date.available2018-08-29T11:57:48Z
dc.date.issued2018
dc.identifier.citationGarcía Rubio, M., Aguilera, P., Lafuente Barquero, J., Ruiz, J.F., Simon, M., Geli, V.,...,Aguilera López, A. (2018). Yra1-bound RNA–DNA hybrids cause orientation-independent transcription– replication collisions and telomere instability. Genes and Development, 32 (13-14), 965-977.
dc.identifier.issn0890-9369es
dc.identifier.issn1549-5477es
dc.identifier.urihttps://hdl.handle.net/11441/78284
dc.description.abstractR loops are an important source of genome instability, largely due to their negative impact on replication progression. Yra1/ALY is an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, but its excess causes lethality and genome instability. Here, we show that, in addition to ssDNA and ssRNA, Yra1 binds RNA–DNA hybrids in vitro and, when artificially overexpressed, can be recruited to chromatin in an RNA– DNA hybrid-dependent manner, stabilizing R loops and converting them into replication obstacles in vivo. Importantly, an excess of Yra1 increases R-loop-mediated genome instability caused by transcription–replication collisions regardless of whether they are codirectional or head-on. It also induces telomere shortening in telomerase-negative cells and accelerates senescence, consistent with a defect in telomere replication. Our results indicate that RNA–DNA hybrids form transiently in cells regardless of replication and, after stabilization by excess Yra1, compromise genome integrity, in agreement with a two-step model of R-loop-mediated genome instability. This work opens new perspectives to understand transcription-associated genome instability in repair-deficient cells, including tumoral cells.es
dc.description.sponsorshipEuropean Research Council ERC2014 AdG669898 TARLOOPes
dc.description.sponsorshipMinisterio de Economía y Competitividad BFU2016-75058-Pes
dc.description.sponsorshipJunta de Andalucía PA12- BIO1238es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherCold Spring Harbor Laboratory Presses
dc.relation.ispartofGenes and Development, 32 (13-14), 965-977.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectR loopes
dc.subjectTelomereses
dc.subjectTranscription-Replication collisiones
dc.subjectYra1es
dc.titleYra1-bound RNA–DNA hybrids cause orientation-independent transcription– replication collisions and telomere instabilityes
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/submittedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Genéticaes
dc.relation.projectIDERC2014 AdG669898 TARLOOPes
dc.relation.projectIDBFU2016-75058-Pes
dc.relation.projectIDPA12- BIO1238es
dc.relation.publisherversionhttp://dx.doi.org/10.1101/gad.311274.117es
dc.identifier.doi10.1101/gad.311274.117es
idus.format.extent37 p.es
dc.journaltitleGenes and Developmentes
dc.publication.volumen32es
dc.publication.issue13-14es
dc.publication.initialPage965es
dc.publication.endPage977es

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