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dc.creatorSantos Pereira, José María
dc.creatorHerrero, Ana B.
dc.creatorGarcía Rubio, María Luisa
dc.creatorMarín Rodríguez, Antonio
dc.creatorMoreno, Sergio
dc.creatorAguilera López, Andrés
dc.date.accessioned2015-10-01T08:41:58Z
dc.date.available2015-10-01T08:41:58Z
dc.date.issued2013
dc.identifier.issn0890-9369es
dc.identifier.issn1549-5477es
dc.identifier.urihttp://hdl.handle.net/11441/29092
dc.description.abstractTranscription is a major obstacle for replication fork (RF) progression and a cause of genome instability. Part of this instability is mediated by cotranscriptional R loops, which are believed to increase by suboptimal assembly of the nascent messenger ribonucleoprotein particle (mRNP). However, no clear evidence exists that heterogeneous nuclear RNPs (hnRNPs), the basic mRNP components, prevent R-loop stabilization. Here we show that yeast Npl3, the most abundant RNA-binding hnRNP, prevents R-loop-mediated genome instability. npl3Δ cells show transcription-dependent and R-loop-dependent hyperrecombination and genome-wide replication obstacles as determined by accumulation of the Rrm3 helicase. Such obstacles preferentially occur at long and highly expressed genes, to which Npl3 is preferentially bound in wild-type cells, and are reduced by RNase H1 overexpression. The resulting replication stress confers hypersensitivity to double-strand break-inducing agents. Therefore, our work demonstrates that mRNP factors are critical for genome integrity and opens the option of using them as therapeutic targets in anti-cancer treatment.es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherCold Spring Harbor Laboratory Presses
dc.relation.ispartofGenes & development, 27(22), 2445-2458es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectR loopses
dc.subjecttranscription-associated genome instabilityes
dc.subjecttranscription–replication conflictses
dc.subjectNpl3es
dc.subjecthnRNPses
dc.subjectDNA damage responsees
dc.titleThe Npl3 hnRNP prevents R-loop-mediated transcription–replication conflicts and genome instabilityes
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Genéticaes
dc.relation.publisherversionhttp://dx.doi.org/10.1101/gad.229880.113es
dc.identifier.doihttp://dx.doi.org/10.1101/gad.229880.113es
dc.identifier.idushttps://idus.us.es/xmlui/handle/11441/29092

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