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TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription

 

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dc.creator Gómez Herreros, Fernando es
dc.creator Zagnoli Vieira, Guido es
dc.creator Ntai, Ioanna es
dc.creator Martínez Macías, María Isabel es
dc.creator Anderson, Rhona M. es
dc.creator Herrero Ruíz, Andrés es
dc.creator Caldecott, Keith W. es
dc.date.accessioned 2017-08-21T10:16:00Z
dc.date.available 2017-08-21T10:16:00Z
dc.date.issued 2017
dc.identifier.citation Gómez Herreros, F., Zagnoli Vieira, G., Ntai, I., Martínez Macías, M.I., Anderson, R.M., Herrero Ruíz, A. y Caldecott, .W. (2017). TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription. Nature Communications, 8 (233), 1-8.
dc.identifier.issn 2041-1723 es
dc.identifier.uri http://hdl.handle.net/11441/63912
dc.description.abstract DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation ‘hotspot’, MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability. es
dc.description.sponsorship España, MINECO RYC-2014-16665 es
dc.description.sponsorship España, MINECO BFU2016-76446-P es
dc.format application/pdf es
dc.language.iso eng es
dc.publisher Nature Publishing Group es
dc.relation.ispartof Nature Communications, 8 (233), 1-8.
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 Internacional *
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ *
dc.title TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription es
dc.type info:eu-repo/semantics/article es
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 info:eu-repo/grantAgreement/MINECO/RYC-2014-16665 es
dc.relation.projectID info:eu-repo/grantAgreement/MINECO/BFU2016-76446-P es
dc.relation.publisherversion http://dx.doi.org/10.1038/s41467-017-00307-y es
dc.identifier.doi 10.1038/s41467-017-00307-y es
idus.format.extent 9 p. es
dc.journaltitle Nature Communications es
dc.publication.volumen 8 es
dc.publication.issue 233 es
dc.publication.initialPage 1 es
dc.publication.endPage 8 es
dc.contributor.funder Ministerio de Economía y Competitividad (MINECO). España
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