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dc.contributor.author
Burgos Barragan, Guillermo  
dc.contributor.author
Wit, Niek  
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Meiser, Johannes  
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Dingler, Felix A.  
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Pietzke, Matthias  
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Mulderrig, Lee  
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Pontel, Lucas Blas  
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Rosado, Ivan V.  
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Brewer, Thomas F.  
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Cordell, Rebecca L.  
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Monks, Paul S.  
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Chang, Christopher J.  
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Vazquez, Alexei  
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Patel, Ketan J.  
dc.date.available
2018-08-02T17:25:20Z  
dc.date.issued
2017-08  
dc.identifier.citation
Burgos Barragan, Guillermo; Wit, Niek; Meiser, Johannes; Dingler, Felix A.; Pietzke, Matthias; et al.; Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism; Nature Publishing Group; Nature; 548; 7669; 8-2017; 549-554  
dc.identifier.issn
0028-0836  
dc.identifier.uri
http://hdl.handle.net/11336/53912  
dc.description.abstract
The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair. Notably, formaldehyde is generated from oxidative decomposition of the folate backbone. Furthermore, we find that formaldehyde detoxification in human cells generates formate, and thereby promotes nucleotide synthesis. This supply of 1C units is sufficient to sustain the growth of cells that are unable to use serine, which is the predominant source of 1C units. These findings identify an unexpected source of formaldehyde and, more generally, indicate that the detoxification of this ubiquitous endogenous genotoxin creates a benign 1C unit that can sustain essential metabolism.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Nature Publishing Group  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Formaldehyde  
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1c Cycle  
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Adh5  
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Fanconi Anemia  
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Otras Ciencias Biológicas  
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Ciencias Biológicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-06-19T15:59:00Z  
dc.journal.volume
548  
dc.journal.number
7669  
dc.journal.pagination
549-554  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
Fil: Burgos Barragan, Guillermo. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido  
dc.description.fil
Fil: Wit, Niek. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido  
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Fil: Meiser, Johannes. Beatson Institute For Cancer Research; Reino Unido  
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Fil: Dingler, Felix A.. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido  
dc.description.fil
Fil: Pietzke, Matthias. Beatson Institute For Cancer Research; Reino Unido  
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Fil: Mulderrig, Lee. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido  
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Fil: Pontel, Lucas Blas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido  
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Fil: Rosado, Ivan V.. Universidad de Sevilla; España  
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Fil: Brewer, Thomas F.. University of California at Berkeley; Estados Unidos  
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Fil: Cordell, Rebecca L.. University of Leicester; Reino Unido  
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Fil: Monks, Paul S.. University of Leicester; Reino Unido  
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Fil: Chang, Christopher J.. University of California at Berkeley; Estados Unidos  
dc.description.fil
Fil: Vazquez, Alexei. Beatson Institute For Cancer Research; Reino Unido  
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Fil: Patel, Ketan J.. University of Cambridge; Estados Unidos. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido  
dc.journal.title
Nature  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1038/nature23481  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nature23481