dc.creator | Salas Armenteros, Irene | es |
dc.creator | Pérez Calero, Carmen | es |
dc.creator | Bayona Feliu, Aleix | es |
dc.creator | Tumini, Emanuela | es |
dc.creator | Luna Varo, Rosa María | es |
dc.creator | Aguilera López, Andrés | es |
dc.date.accessioned | 2019-06-13T14:33:47Z | |
dc.date.available | 2019-06-13T14:33:47Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Salas Armenteros, I., Pérez Calero, C., Bayona Feliu, A., Tumini, E., Luna Varo, R.M. y Aguilera López, A. (2017). Human THO–Sin3A interaction reveals new mechanisms to prevent R-loops that cause genome instability. EMBO Journal, 36 (23), 3532-3547. | |
dc.identifier.issn | 0261-4189 | es |
dc.identifier.issn | 1460-2075 | es |
dc.identifier.uri | https://hdl.handle.net/11441/87419 | |
dc.description.abstract | R-loops, formed by co-transcriptional DNA–RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent R-loop accumulation centers on the conserved THO/TREX complex, an RNA-binding factor involved in transcription elongation and RNA export that contributes to messenger ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear. To understand how THO restrains harmful R-loops, we searched for new THO-interacting factors. We found that human THO interacts with the Sin3A histone deacetylase complex to suppress co-transcriptional R-loops, DNA damage, and replication impairment. Functional analyses show that histone hypo-acetylation prevents accumulation of harmful R-loops and RNA-mediated genomic instability. Diminished histone deacetylase activity in THO- and Sin3A-depleted cell lines correlates with increased R-loop formation, genomic instability, and replication fork stalling. Our study thus uncovers physical and functional crosstalk between RNA-binding factors and chromatin modifiers with a major role in preventing R-loop formation and RNA-mediated genome instability. | es |
dc.description.sponsorship | European Research Council ERC2014 AdG669898 TARLOOP | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad BFU2013-42918-P, BFU2016-75058-P | es |
dc.description.sponsorship | Junta de Andalucía BIO1238 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Wiley-Blackwell | es |
dc.relation.ispartof | EMBO Journal, 36 (23), 3532-3547. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | DNA–RNA hybrids | es |
dc.subject | Genome instability | es |
dc.subject | Histone acetylation | es |
dc.subject | Sin3A deacetylase | es |
dc.subject | THO/TREX | es |
dc.title | Human THO–Sin3A interaction reveals new mechanisms to prevent R-loops that cause genome instability | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.projectID | ERC2014 AdG669898 TARLOOP | es |
dc.relation.projectID | BFU2013-42918-P | es |
dc.relation.projectID | BFU2016-75058-P | es |
dc.relation.projectID | BIO1238 | es |
dc.relation.publisherversion | http://dx.doi.org/10.15252/embj.201797208 | es |
dc.identifier.doi | 10.15252/embj.201797208 | es |
idus.format.extent | 16 p. | es |
dc.journaltitle | EMBO Journal | es |
dc.publication.volumen | 36 | es |
dc.publication.issue | 23 | es |
dc.publication.initialPage | 3532 | es |
dc.publication.endPage | 3547 | es |