dc.creator | Tumini, Emanuela | es |
dc.creator | Herrera Moyano, Emilia | es |
dc.creator | San Martín Alonso, Marta | es |
dc.creator | Barroso Ceballos, Sonia Inés | es |
dc.creator | Galmarini, Carlos María | es |
dc.creator | Aguilera López, Andrés | es |
dc.date.accessioned | 2020-10-02T17:53:03Z | |
dc.date.available | 2020-10-02T17:53:03Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Tumini, E., Herrera Moyano, E., San Martín Alonso, M., Barroso Ceballos, S.I., Galmarini, C.M. y Aguilera López, A. (2019). The antitumor drugs trabectedin and lurbinectedin induce transcription-dependent replication stress and genome instability. The antitumor drugs trabectedin and lurbinectedin induce transcription-dependent replication stress and genome instability, 17 (3), 773-782. | |
dc.identifier.issn | 1541-7786 | es |
dc.identifier.issn | 1557-3125 | es |
dc.identifier.uri | https://hdl.handle.net/11441/101683 | |
dc.description.abstract | R-loops are a major source of replication stress, DNA damage, and genome instability, which are major hallmarks of cancer cells. Accordingly, growing evidence suggests that R-loops may also be related to cancer. Here we show that R-loops play an important role in the cellular response to trabectedin (ET743), an anticancer drug from marine origin and its derivative lurbinectedin (PM01183). Trabectedin and lurbinectedin induced RNA–DNA hybrid-dependent DNA damage in HeLa cells, causing replication impairment and genome instability. We also show that high levels of R-loops increase cell sensitivity to trabectedin. In addition, trabectedin led to transcription-dependent FANCD2 foci accumulation, which was suppressed by RNase H1 overexpression. In yeast, trabectedin and lurbinectedin increased the presence of Rad52 foci, a marker of DNA damage, in an R-loop–dependent manner. In addition to providing new insights into the mechanisms of action of these drugs, our study reveals that R-loops could be targeted by anticancer agents. Given the increasing evidence that R-loops occur all over the genome, the ability of lurbinectedin and trabectedin to act on them may contribute to enhance their efficacy, opening the possibility that R-loops might be a feature shared by specific cancers. Implications: The data presented in this study provide the new concept that R-loops are important cellular factors that contribute to trabectedin and lurbinectedin anticancer activity. | es |
dc.description.sponsorship | European Research Council ERC2014 AdG669898 TARLOOP | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad BFU2016-75058-P | es |
dc.description.sponsorship | PharmaMar PRJ201402213 | es |
dc.format | application/pdf | es |
dc.format.extent | 36 p. | es |
dc.language.iso | eng | es |
dc.publisher | American Association for Cancer Research | es |
dc.relation.ispartof | The antitumor drugs trabectedin and lurbinectedin induce transcription-dependent replication stress and genome instability, 17 (3), 773-782. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Trabectedin | es |
dc.subject | Lurbinectedin | es |
dc.subject | R-loops | es |
dc.subject | Genome instability | es |
dc.subject | Cancer | es |
dc.title | The antitumor drugs trabectedin and lurbinectedin induce transcription-dependent replication stress and genome instability | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/acceptedVersion | 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 | BFU2016-75058-P | es |
dc.relation.projectID | PRJ201402213 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1158/1541-7786.MCR-18-0575 | es |
dc.identifier.doi | 10.1158/1541-7786.MCR-18-0575 | es |
dc.journaltitle | The antitumor drugs trabectedin and lurbinectedin induce transcription-dependent replication stress and genome instability | es |
dc.publication.volumen | 17 | es |
dc.publication.issue | 3 | es |
dc.publication.initialPage | 773 | es |
dc.publication.endPage | 782 | es |