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dc.creatorRuiz Pérez, José Francisco
dc.creatorGómez González, Belén
dc.creatorAguilera López, Andrés
dc.date.accessioned2015-10-02T10:53:37Z
dc.date.available2015-10-02T10:53:37Z
dc.date.issued2011
dc.identifier.citationRuiz Pérez, J.F., Gómez González, B. y Aguilera López, A. (2011). AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants. PLoS Genetics, 7 (2), e1002009.
dc.identifier.issn1553-7390es
dc.identifier.issn1553-7404es
dc.identifier.urihttp://hdl.handle.net/11441/29114
dc.description.abstractTranscription of the switch (S) regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID), triggering class switch recombination (CSR), as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs) which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ). AID–induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID–mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID–mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherPublic Library of Sciencees
dc.relation.ispartofPLoS Genetics, 7 (2), e1002009.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectTranslocationses
dc.subjectChromosomeses
dc.subjectB cellses
dc.subjectDNA transcriptiones
dc.subjectSequence motif analysises
dc.subjectIntronses
dc.subjectBiosynthesises
dc.subjectDNA recombinationes
dc.titleAID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutantses
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Genéticaes
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Moleculares
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pgen.1002009es
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1002009es
dc.journaltitlePLoS Genetics
dc.publication.volumen7
dc.publication.issue2
dc.publication.initialPagee1002009
dc.identifier.idushttps://idus.us.es/xmlui/handle/11441/29114

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