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dc.contributor.authorGarcía-Pichardo, Desiré-
dc.contributor.authorCañas, Juan C.-
dc.contributor.authorGarcía-Rubio, María L.-
dc.contributor.authorGómez-González, Belén-
dc.contributor.authorRondón, Ana G.-
dc.contributor.authorAguilera, Andrés-
dc.date.accessioned2018-06-04T07:54:29Z-
dc.date.available2018-06-04T07:54:29Z-
dc.date.issued2017-
dc.identifierdoi: 10.1016/j.molcel.2017.05.014-
dc.identifiere-issn: 1097-4164-
dc.identifierissn: 1097-2765-
dc.identifier.citationMolecular Cell 66(5): 597-609.e5 (2017)-
dc.identifier.urihttp://hdl.handle.net/10261/165552-
dc.description.abstractR loops have positive physiological roles, but they can also be deleterious by causing genome instability, and the mechanisms for this are unknown. Here we identified yeast histone H3 and H4 mutations that facilitate R loops but do not cause instability. R loops containing single-stranded DNA (ssDNA), versus RNA-DNA hybrids alone, were demonstrated using ssDNA-specific human AID and bisulfite. Notably, they are similar size regardless of whether or not they induce genome instability. Contrary to mutants causing R loop-mediated instability, these histone mutants do not accumulate H3 serine-10 phosphate (H3S10-P). We propose a two-step mechanism in which, first, an altered chromatin facilitates R loops, and second, chromatin is modified, including H3S10-P, as a requisite for compromising genome integrity. Consistently, these histone mutations suppress the high H3S10 phosphorylation and genomic instability of hpr1 and sen1 mutants. Therefore, contrary to what was previously believed, R loops do not cause genome instability by themselves.-
dc.description.sponsorshipResearch was supported by the European Research Council (ERC2014 AdG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (BFU2013-42918-P and BFU2016-75058-P), and the European Union (FEDER). D.G.-P. and J.C.C. were supported by predoctoral training grants from the Spanish Ministry of Economy and Competitiveness, B.G.-G. by the Scientific Foundation of the Spanish Association Against Cancer, and A.G.R. by the Ramón y Cajal Program of Ministry of Economy and Competitiveness.-
dc.publisherElsevier-
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75058-P-
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-42918-P-
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/669898-
dc.rightsclosedAccess-
dc.subjectChromatin compaction-
dc.subjectCromatin-
dc.subjectHistones H3 and H4-
dc.subjectChromosome fragility-
dc.subjectH3 serine-10 phosphorylation-
dc.subjectGenome instability-
dc.subjectR loops-
dc.subjectRNA-DNA hybrids-
dc.titleHistone mutants separate R loop formation from genome instability induction-
dc.typeartículo-
dc.identifier.doi10.1016/j.molcel.2017.05.014-
dc.date.updated2018-06-04T07:54:29Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderEuropean Commission-
dc.contributor.funderEuropean Research Council-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderFundación Científica Asociación Española Contra el Cáncer-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002704es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000781es_ES
dc.identifier.pmid28575656-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
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