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Artículo
The Npl3 hnRNP prevents R-loop-mediated transcription–replication conflicts and genome instability
dc.creator | Santos Pereira, José María | |
dc.creator | Herrero, Ana B. | |
dc.creator | García Rubio, María Luisa | |
dc.creator | Marín Rodríguez, Antonio | |
dc.creator | Moreno, Sergio | |
dc.creator | Aguilera López, Andrés | |
dc.date.accessioned | 2015-10-01T08:41:58Z | |
dc.date.available | 2015-10-01T08:41:58Z | |
dc.date.issued | 2013 | |
dc.identifier.issn | 0890-9369 | es |
dc.identifier.issn | 1549-5477 | es |
dc.identifier.uri | http://hdl.handle.net/11441/29092 | |
dc.description.abstract | Transcription 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.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Cold Spring Harbor Laboratory Press | es |
dc.relation.ispartof | Genes & development, 27(22), 2445-2458 | es |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | R loops | es |
dc.subject | transcription-associated genome instability | es |
dc.subject | transcription–replication conflicts | es |
dc.subject | Npl3 | es |
dc.subject | hnRNPs | es |
dc.subject | DNA damage response | es |
dc.title | The Npl3 hnRNP prevents R-loop-mediated transcription–replication conflicts and genome instability | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.publisherversion | http://dx.doi.org/10.1101/gad.229880.113 | es |
dc.identifier.doi | http://dx.doi.org/10.1101/gad.229880.113 | es |
dc.identifier.idus | https://idus.us.es/xmlui/handle/11441/29092 |
Ficheros | Tamaño | Formato | Ver | Descripción |
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2445.full.pdf | 1.388Mb | ![]() | Ver/ | |