DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering
Accumulation 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-defecti...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2019
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/22636
- Acceso en línea:
- https://doi.org/10.1038/s41467-019-12640-5
https://repository.urosario.edu.co/handle/10336/22636
- Palabra clave:
- 1 phosphofructokinase
Antimycin a1
Carbonyl cyanide 4 (trifluoromethoxy)phenylhydrazone
Glucose 6 phosphate dehydrogenase
Glucose transporter
Glutathione
Oligomycin
Pentose phosphate
Reduced nicotinamide adenine dinucleotide phosphate
Rotenone
Sugar phosphate
Adenosine triphosphate
Antioxidant
Dna binding protein
Dna excision repair protein ercc-5
Endonuclease
Nicotinamide adenine dinucleotide phosphate
Nuclear protein
Transcription factor
Aging
Antioxidant
Bioenergetics
Buffering
Dna
Enzyme activity
Metabolism
Phosphate
Redox conditions
Stress analysis
Ampk signaling
Animal experiment
Animal model
Antioxidant activity
Article
Bioenergy
Bioinformatics
Cell isolation
Cockayne syndrome
Cycloaddition
Dna damage
Dna repair
Dna transcription
Down regulation
Drug potentiation
Enzyme activity
Enzyme metabolism
Excision repair
Female
Flow cytometry
Gene expression level
Gene mutation
Genomic instability
Glycolysis
High performance liquid chromatography
Male
Metabolic activity assay
Metabolic flux analysis
Mitochondrial respiration
Mouse
Nonhuman
Nuclear reprogramming
Oxygen consumption
Pentose phosphate cycle
Peritoneum
Polymerase chain reaction
Protein phosphorylation
Redox stress
Rna isolation
Rna synthesis
Signal transduction
Skin biopsy
Skin fibroblast
Transcription coupled dna repair
Upregulation
Allosterism
Animal
Cytology
Dna damage
Fibroblast
Genetic transcription
Genetics
Knockout mouse
Metabolism
Metabolomics
Oxidation reduction reaction
Physiology
Skin
Animalia
Mus
Adenosine triphosphate
Allosteric regulation
Animals
Antioxidants
Cockayne syndrome
Dna damage
Dna repair
Dna-binding proteins
Endonucleases
Fibroblasts
Genomic instability
Glycolysis
Metabolomics
Mice
Nadp
Nuclear proteins
Oxidation-reduction
Pentose phosphate pathway
Skin
Transcription factors
knockout
mouse
genetic
Ercc1 protein
Mice
Transcription
- Rights
- License
- Abierto (Texto Completo)
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dc.title.spa.fl_str_mv |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering |
title |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering |
spellingShingle |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering 1 phosphofructokinase Antimycin a1 Carbonyl cyanide 4 (trifluoromethoxy)phenylhydrazone Glucose 6 phosphate dehydrogenase Glucose transporter Glutathione Oligomycin Pentose phosphate Reduced nicotinamide adenine dinucleotide phosphate Rotenone Sugar phosphate Adenosine triphosphate Antioxidant Dna binding protein Dna excision repair protein ercc-5 Endonuclease Nicotinamide adenine dinucleotide phosphate Nuclear protein Transcription factor Aging Antioxidant Bioenergetics Buffering Dna Enzyme activity Metabolism Phosphate Redox conditions Stress analysis Ampk signaling Animal experiment Animal model Antioxidant activity Article Bioenergy Bioinformatics Cell isolation Cockayne syndrome Cycloaddition Dna damage Dna repair Dna transcription Down regulation Drug potentiation Enzyme activity Enzyme metabolism Excision repair Female Flow cytometry Gene expression level Gene mutation Genomic instability Glycolysis High performance liquid chromatography Male Metabolic activity assay Metabolic flux analysis Mitochondrial respiration Mouse Nonhuman Nuclear reprogramming Oxygen consumption Pentose phosphate cycle Peritoneum Polymerase chain reaction Protein phosphorylation Redox stress Rna isolation Rna synthesis Signal transduction Skin biopsy Skin fibroblast Transcription coupled dna repair Upregulation Allosterism Animal Cytology Dna damage Fibroblast Genetic transcription Genetics Knockout mouse Metabolism Metabolomics Oxidation reduction reaction Physiology Skin Animalia Mus Adenosine triphosphate Allosteric regulation Animals Antioxidants Cockayne syndrome Dna damage Dna repair Dna-binding proteins Endonucleases Fibroblasts Genomic instability Glycolysis Metabolomics Mice Nadp Nuclear proteins Oxidation-reduction Pentose phosphate pathway Skin Transcription factors knockout mouse genetic Ercc1 protein Mice Transcription |
title_short |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering |
title_full |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering |
title_fullStr |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering |
title_full_unstemmed |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering |
title_sort |
DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering |
dc.subject.keyword.spa.fl_str_mv |
1 phosphofructokinase Antimycin a1 Carbonyl cyanide 4 (trifluoromethoxy)phenylhydrazone Glucose 6 phosphate dehydrogenase Glucose transporter Glutathione Oligomycin Pentose phosphate Reduced nicotinamide adenine dinucleotide phosphate Rotenone Sugar phosphate Adenosine triphosphate Antioxidant Dna binding protein Dna excision repair protein ercc-5 Endonuclease Nicotinamide adenine dinucleotide phosphate Nuclear protein Transcription factor Aging Antioxidant Bioenergetics Buffering Dna Enzyme activity Metabolism Phosphate Redox conditions Stress analysis Ampk signaling Animal experiment Animal model Antioxidant activity Article Bioenergy Bioinformatics Cell isolation Cockayne syndrome Cycloaddition Dna damage Dna repair Dna transcription Down regulation Drug potentiation Enzyme activity Enzyme metabolism Excision repair Female Flow cytometry Gene expression level Gene mutation Genomic instability Glycolysis High performance liquid chromatography Male Metabolic activity assay Metabolic flux analysis Mitochondrial respiration Mouse Nonhuman Nuclear reprogramming Oxygen consumption Pentose phosphate cycle Peritoneum Polymerase chain reaction Protein phosphorylation Redox stress Rna isolation Rna synthesis Signal transduction Skin biopsy Skin fibroblast Transcription coupled dna repair Upregulation Allosterism Animal Cytology Dna damage Fibroblast Genetic transcription Genetics Knockout mouse Metabolism Metabolomics Oxidation reduction reaction Physiology Skin Animalia Mus Adenosine triphosphate Allosteric regulation Animals Antioxidants Cockayne syndrome Dna damage Dna repair Dna-binding proteins Endonucleases Fibroblasts Genomic instability Glycolysis Metabolomics Mice Nadp Nuclear proteins Oxidation-reduction Pentose phosphate pathway Skin Transcription factors |
topic |
1 phosphofructokinase Antimycin a1 Carbonyl cyanide 4 (trifluoromethoxy)phenylhydrazone Glucose 6 phosphate dehydrogenase Glucose transporter Glutathione Oligomycin Pentose phosphate Reduced nicotinamide adenine dinucleotide phosphate Rotenone Sugar phosphate Adenosine triphosphate Antioxidant Dna binding protein Dna excision repair protein ercc-5 Endonuclease Nicotinamide adenine dinucleotide phosphate Nuclear protein Transcription factor Aging Antioxidant Bioenergetics Buffering Dna Enzyme activity Metabolism Phosphate Redox conditions Stress analysis Ampk signaling Animal experiment Animal model Antioxidant activity Article Bioenergy Bioinformatics Cell isolation Cockayne syndrome Cycloaddition Dna damage Dna repair Dna transcription Down regulation Drug potentiation Enzyme activity Enzyme metabolism Excision repair Female Flow cytometry Gene expression level Gene mutation Genomic instability Glycolysis High performance liquid chromatography Male Metabolic activity assay Metabolic flux analysis Mitochondrial respiration Mouse Nonhuman Nuclear reprogramming Oxygen consumption Pentose phosphate cycle Peritoneum Polymerase chain reaction Protein phosphorylation Redox stress Rna isolation Rna synthesis Signal transduction Skin biopsy Skin fibroblast Transcription coupled dna repair Upregulation Allosterism Animal Cytology Dna damage Fibroblast Genetic transcription Genetics Knockout mouse Metabolism Metabolomics Oxidation reduction reaction Physiology Skin Animalia Mus Adenosine triphosphate Allosteric regulation Animals Antioxidants Cockayne syndrome Dna damage Dna repair Dna-binding proteins Endonucleases Fibroblasts Genomic instability Glycolysis Metabolomics Mice Nadp Nuclear proteins Oxidation-reduction Pentose phosphate pathway Skin Transcription factors knockout mouse genetic Ercc1 protein Mice Transcription |
dc.subject.keyword.eng.fl_str_mv |
knockout mouse genetic Ercc1 protein Mice Transcription |
description |
Accumulation 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). |
publishDate |
2019 |
dc.date.created.spa.fl_str_mv |
2019 |
dc.date.accessioned.none.fl_str_mv |
2020-05-25T23:57:15Z |
dc.date.available.none.fl_str_mv |
2020-05-25T23:57:15Z |
dc.type.eng.fl_str_mv |
article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.spa.spa.fl_str_mv |
Artículo |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1038/s41467-019-12640-5 |
dc.identifier.issn.none.fl_str_mv |
20411723 |
dc.identifier.uri.none.fl_str_mv |
https://repository.urosario.edu.co/handle/10336/22636 |
url |
https://doi.org/10.1038/s41467-019-12640-5 https://repository.urosario.edu.co/handle/10336/22636 |
identifier_str_mv |
20411723 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.citationIssue.none.fl_str_mv |
No. 1 |
dc.relation.citationTitle.none.fl_str_mv |
Nature Communications |
dc.relation.citationVolume.none.fl_str_mv |
Vol. 10 |
dc.relation.ispartof.spa.fl_str_mv |
Nature Communications, ISSN:20411723, Vol.10, No.1 (2019) |
dc.relation.uri.spa.fl_str_mv |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074162272&doi=10.1038%2fs41467-019-12640-5&partnerID=40&md5=7c7a724f4d871305d5f6cbed2d0b4284 |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
rights_invalid_str_mv |
Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
Nature Publishing Group |
institution |
Universidad del Rosario |
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reponame:Repositorio Institucional EdocUR |
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feb567b4-24f5-4f34-bcfc-f77b55a86345-1a1e3ab7b-916d-47ab-bff4-200631c43fdb-17f6bc8c5-2bb6-4298-8989-0cc5bceaa45d-18f176f9f-7e4d-46e4-8ace-e21129276137-1fe1aaba9-c808-4395-80be-f9ca6d292f96-1c86d0127-39d5-4490-b19e-a2bb27630849-1b4bca836-a627-4d2d-9e53-03aac3bcc623-1d4dce881-5144-462e-9a45-654fb3295bcb-1be6aa57e-ec05-45f4-a4d1-cfd9afbe0bc7-185c61937-a38b-4efb-a930-e829d50c0510-1be52aa3c-3396-423f-bde8-1eb50fe1a6ab-1774599a3-dc72-4a2a-8d3f-fde7b8c3c322-1145ba046-cf16-4008-aa32-00e890103c8d-1420d4109-ff25-490b-af89-aa9e542d3396-1b2155f02-3f96-46dc-b29f-de1c2f61d23a-1067f6dd1-a2e7-41b1-a4dc-f6bbabdf0753-122d7b8d2-0adb-4ad5-b752-5563bbd8b8b8-13d6f06c3-dd73-47c8-9d55-e4ad8447d738-1763272336002020-05-25T23:57:15Z2020-05-25T23:57:15Z2019Accumulation 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).application/pdfhttps://doi.org/10.1038/s41467-019-12640-520411723https://repository.urosario.edu.co/handle/10336/22636engNature Publishing GroupNo. 1Nature CommunicationsVol. 10Nature Communications, ISSN:20411723, Vol.10, No.1 (2019)https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074162272&doi=10.1038%2fs41467-019-12640-5&partnerID=40&md5=7c7a724f4d871305d5f6cbed2d0b4284Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocUR1 phosphofructokinaseAntimycin a1Carbonyl cyanide 4 (trifluoromethoxy)phenylhydrazoneGlucose 6 phosphate dehydrogenaseGlucose transporterGlutathioneOligomycinPentose phosphateReduced nicotinamide adenine dinucleotide phosphateRotenoneSugar phosphateAdenosine triphosphateAntioxidantDna binding proteinDna excision repair protein ercc-5EndonucleaseNicotinamide adenine dinucleotide phosphateNuclear proteinTranscription factorAgingAntioxidantBioenergeticsBufferingDnaEnzyme activityMetabolismPhosphateRedox conditionsStress analysisAmpk signalingAnimal experimentAnimal modelAntioxidant activityArticleBioenergyBioinformaticsCell isolationCockayne syndromeCycloadditionDna damageDna repairDna transcriptionDown regulationDrug potentiationEnzyme activityEnzyme metabolismExcision repairFemaleFlow cytometryGene expression levelGene mutationGenomic instabilityGlycolysisHigh performance liquid chromatographyMaleMetabolic activity assayMetabolic flux analysisMitochondrial respirationMouseNonhumanNuclear reprogrammingOxygen consumptionPentose phosphate cyclePeritoneumPolymerase chain reactionProtein phosphorylationRedox stressRna isolationRna synthesisSignal transductionSkin biopsySkin fibroblastTranscription coupled dna repairUpregulationAllosterismAnimalCytologyDna damageFibroblastGenetic transcriptionGeneticsKnockout mouseMetabolismMetabolomicsOxidation reduction reactionPhysiologySkinAnimaliaMusAdenosine triphosphateAllosteric regulationAnimalsAntioxidantsCockayne syndromeDna damageDna repairDna-binding proteinsEndonucleasesFibroblastsGenomic instabilityGlycolysisMetabolomicsMiceNadpNuclear proteinsOxidation-reductionPentose phosphate pathwaySkinTranscription factorsknockoutmousegeneticErcc1 proteinMiceTranscriptionDNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant bufferingarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Milanese, ChiaraBombardieri, Cíntia R.Sepe, SaraBarnhoorn, SanderCaruso, DonatellaAudano, MatteoPedretti, SilviaVermeij, Wilbert P.Brandt, Renata M. C.Gyenis, AkosWamelink, Mirjam M.de Wit, Annelieke S.Janssens, Roel C.Leen, Renévan Kuilenburg, André B. P.Mitro, NicoHoeijmakers, Jan H. J.Mastroberardino, Pier G.Payan-Gomez, CesarORIGINALs41467-019-12640-5.pdfapplication/pdf2921302https://repository.urosario.edu.co/bitstreams/b039efc5-5db6-4d77-9fb8-36ac51b79db3/downloade99c83ad4ad385973c06314ecb680f01MD51TEXTs41467-019-12640-5.pdf.txts41467-019-12640-5.pdf.txtExtracted texttext/plain103749https://repository.urosario.edu.co/bitstreams/ab1b431a-6826-4259-86c9-102e8daf753b/download57502ee53b04f959eea25f213c2797a4MD52THUMBNAILs41467-019-12640-5.pdf.jpgs41467-019-12640-5.pdf.jpgGenerated Thumbnailimage/jpeg3889https://repository.urosario.edu.co/bitstreams/b437f694-e7a2-483c-952d-9e0d9b6e1bd3/downloadc2a742f3bd4c70fdb529064891a3cd32MD5310336/22636oai:repository.urosario.edu.co:10336/226362022-05-02 07:37:20.532834https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co |