Mostrar el registro sencillo del ítem

dc.contributor.author
Burgos Barragan, Guillermo
dc.contributor.author
Wit, Niek
dc.contributor.author
Meiser, Johannes
dc.contributor.author
Dingler, Felix A.
dc.contributor.author
Pietzke, Matthias
dc.contributor.author
Mulderrig, Lee
dc.contributor.author
Pontel, Lucas Blas
dc.contributor.author
Rosado, Ivan V.
dc.contributor.author
Brewer, Thomas F.
dc.contributor.author
Cordell, Rebecca L.
dc.contributor.author
Monks, Paul S.
dc.contributor.author
Chang, Christopher J.
dc.contributor.author
Vazquez, Alexei
dc.contributor.author
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/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Formaldehyde
dc.subject
1c Cycle
dc.subject
Adh5
dc.subject
Fanconi Anemia
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
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
dc.description.fil
Fil: Meiser, Johannes. Beatson Institute For Cancer Research; Reino Unido
dc.description.fil
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
dc.description.fil
Fil: Mulderrig, Lee. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido
dc.description.fil
Fil: Pontel, Lucas Blas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. The Medical Research Council Laboratory Of Molecular Biology; Reino Unido
dc.description.fil
Fil: Rosado, Ivan V.. Universidad de Sevilla; España
dc.description.fil
Fil: Brewer, Thomas F.. University of California at Berkeley; Estados Unidos
dc.description.fil
Fil: Cordell, Rebecca L.. University of Leicester; Reino Unido
dc.description.fil
Fil: Monks, Paul S.. University of Leicester; Reino Unido
dc.description.fil
Fil: Chang, Christopher J.. University of California at Berkeley; Estados Unidos
dc.description.fil
Fil: Vazquez, Alexei. Beatson Institute For Cancer Research; Reino Unido
dc.description.fil
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


Archivos asociados

Documento no disponible

Comunidades y colecciones

Mostrar el registro sencillo del ítem