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DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering

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dc.creatorMilanese, Chiaraspa
dc.creatorBombardieri, Cíntia R.spa
dc.creatorSepe, Saraspa
dc.creatorBarnhoorn, Sanderspa
dc.creatorPayan-Gomez, Cesar
dc.creatorCaruso, Donatellaspa
dc.creatorAudano, Matteospa
dc.creatorPedretti, Silviaspa
dc.creatorVermeij, Wilbert P.spa
dc.creatorBrandt, Renata M. C.spa
dc.creatorGyenis, Akosspa
dc.creatorWamelink, Mirjam M.spa
dc.creatorde Wit, Annelieke S.spa
dc.creatorJanssens, Roel C.spa
dc.creatorLeen, Renéspa
dc.creatorvan Kuilenburg, André B. P.spa
dc.creatorMitro, Nicospa
dc.creatorHoeijmakers, Jan H. J.spa
dc.creatorMastroberardino, Pier G.spa
dc.date.accessioned2020-05-25T23:57:15Z
dc.date.available2020-05-25T23:57:15Z
dc.date.created2019spa
dc.description.abstractAccumulation of DNA lesions causing transcription stress is associated with natural and accelerated aging and culminates with profound metabolic alterations. Our understanding of the mechanisms governing metabolic redesign upon genomic instability, however, is highly rudimentary. Using Ercc1-defective mice and Xpg knock-out mice, we demonstrate that combined defects in transcription-coupled DNA repair (TCR) and in nucleotide excision repair (NER) directly affect bioenergetics due to declined transcription, leading to increased ATP levels. This in turn inhibits glycolysis allosterically and favors glucose rerouting through the pentose phosphate shunt, eventually enhancing production of NADPH-reducing equivalents. In NER/TCR-defective mutants, augmented NADPH is not counterbalanced by increased production of pro-oxidants and thus pentose phosphate potentiation culminates in an over-reduced redox state. Skin fibroblasts from the TCR disease Cockayne syndrome confirm results in animal models. Overall, these findings unravel a mechanism connecting DNA damage and transcriptional stress to metabolic redesign and protective antioxidant defenses. © 2019, The Author(s).eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1038/s41467-019-12640-5
dc.identifier.issn20411723
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22636
dc.language.isoengspa
dc.publisherNature Publishing Groupspa
dc.relation.citationIssueNo. 1
dc.relation.citationTitleNature Communications
dc.relation.citationVolumeVol. 10
dc.relation.ispartofNature Communications, ISSN:20411723, Vol.10, No.1 (2019)spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85074162272&doi=10.1038%2fs41467-019-12640-5&partnerID=40&md5=7c7a724f4d871305d5f6cbed2d0b4284spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keyword1 phosphofructokinasespa
dc.subject.keywordAntimycin a1spa
dc.subject.keywordCarbonyl cyanide 4 (trifluoromethoxy)phenylhydrazonespa
dc.subject.keywordGlucose 6 phosphate dehydrogenasespa
dc.subject.keywordGlucose transporterspa
dc.subject.keywordGlutathionespa
dc.subject.keywordOligomycinspa
dc.subject.keywordPentose phosphatespa
dc.subject.keywordReduced nicotinamide adenine dinucleotide phosphatespa
dc.subject.keywordRotenonespa
dc.subject.keywordSugar phosphatespa
dc.subject.keywordAdenosine triphosphatespa
dc.subject.keywordAntioxidantspa
dc.subject.keywordDna binding proteinspa
dc.subject.keywordDna excision repair protein ercc-5spa
dc.subject.keywordEndonucleasespa
dc.subject.keywordErcc1 proteineng
dc.subject.keywordNicotinamide adenine dinucleotide phosphatespa
dc.subject.keywordNuclear proteinspa
dc.subject.keywordTranscription factorspa
dc.subject.keywordAgingspa
dc.subject.keywordAntioxidantspa
dc.subject.keywordBioenergeticsspa
dc.subject.keywordBufferingspa
dc.subject.keywordDnaspa
dc.subject.keywordEnzyme activityspa
dc.subject.keywordMetabolismspa
dc.subject.keywordPhosphatespa
dc.subject.keywordRedox conditionsspa
dc.subject.keywordStress analysisspa
dc.subject.keywordAmpk signalingspa
dc.subject.keywordAnimal experimentspa
dc.subject.keywordAnimal modelspa
dc.subject.keywordAntioxidant activityspa
dc.subject.keywordArticlespa
dc.subject.keywordBioenergyspa
dc.subject.keywordBioinformaticsspa
dc.subject.keywordCell isolationspa
dc.subject.keywordCockayne syndromespa
dc.subject.keywordCycloadditionspa
dc.subject.keywordDna damagespa
dc.subject.keywordDna repairspa
dc.subject.keywordDna transcriptionspa
dc.subject.keywordDown regulationspa
dc.subject.keywordDrug potentiationspa
dc.subject.keywordEnzyme activityspa
dc.subject.keywordEnzyme metabolismspa
dc.subject.keywordExcision repairspa
dc.subject.keywordFemalespa
dc.subject.keywordFlow cytometryspa
dc.subject.keywordGene expression levelspa
dc.subject.keywordGene mutationspa
dc.subject.keywordGenomic instabilityspa
dc.subject.keywordGlycolysisspa
dc.subject.keywordHigh performance liquid chromatographyspa
dc.subject.keywordMalespa
dc.subject.keywordMetabolic activity assayspa
dc.subject.keywordMetabolic flux analysisspa
dc.subject.keywordMitochondrial respirationspa
dc.subject.keywordMousespa
dc.subject.keywordNonhumanspa
dc.subject.keywordNuclear reprogrammingspa
dc.subject.keywordOxygen consumptionspa
dc.subject.keywordPentose phosphate cyclespa
dc.subject.keywordPeritoneumspa
dc.subject.keywordPolymerase chain reactionspa
dc.subject.keywordProtein phosphorylationspa
dc.subject.keywordRedox stressspa
dc.subject.keywordRna isolationspa
dc.subject.keywordRna synthesisspa
dc.subject.keywordSignal transductionspa
dc.subject.keywordSkin biopsyspa
dc.subject.keywordSkin fibroblastspa
dc.subject.keywordTranscription coupled dna repairspa
dc.subject.keywordUpregulationspa
dc.subject.keywordAllosterismspa
dc.subject.keywordAnimalspa
dc.subject.keywordCytologyspa
dc.subject.keywordDna damagespa
dc.subject.keywordFibroblastspa
dc.subject.keywordGenetic transcriptionspa
dc.subject.keywordGeneticsspa
dc.subject.keywordKnockout mousespa
dc.subject.keywordMetabolismspa
dc.subject.keywordMetabolomicsspa
dc.subject.keywordOxidation reduction reactionspa
dc.subject.keywordPhysiologyspa
dc.subject.keywordSkinspa
dc.subject.keywordAnimaliaspa
dc.subject.keywordMusspa
dc.subject.keywordAdenosine triphosphatespa
dc.subject.keywordAllosteric regulationspa
dc.subject.keywordAnimalsspa
dc.subject.keywordAntioxidantsspa
dc.subject.keywordCockayne syndromespa
dc.subject.keywordDna damagespa
dc.subject.keywordDna repairspa
dc.subject.keywordDna-binding proteinsspa
dc.subject.keywordEndonucleasesspa
dc.subject.keywordFibroblastsspa
dc.subject.keywordGenomic instabilityspa
dc.subject.keywordGlycolysisspa
dc.subject.keywordMetabolomicsspa
dc.subject.keywordMicespa
dc.subject.keywordMiceeng
dc.subject.keywordNadpspa
dc.subject.keywordNuclear proteinsspa
dc.subject.keywordOxidation-reductionspa
dc.subject.keywordPentose phosphate pathwayspa
dc.subject.keywordSkinspa
dc.subject.keywordTranscription factorsspa
dc.subject.keywordTranscriptioneng
dc.titleDNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant bufferingspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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