2026-06-14T05:06:42Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/102642024-11-29T14:19:10Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Lopez-Contreras, Andres J
author
Specks, Julia
author
Barlow, Jacqueline H
author
Ambrogio, Chiara
author
Desler, Claus
author
Vikingsson, Svante
author
Rodrigo-Perez, Sara
author
Green, Henrik
author
Rasmussen, Lene Juel
author
Nussenzweig, André
author
Fernandez-Capetillo, Oscar
funder
Asociación Española Contra el Cáncer
funder
Swedish Research Council
funder
Botín Foundation
funder
Banco Santander
funder
Ministerio de Economía y Competitividad (España)
funder
Worldwide Cancer Research
funder
Fundación La Marató TV3
funder
Howard Hughes Medical Institute
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Det Frie Forskningsrad (DFF)
funder
Danmarks Grundforskningsfond
2020-06-03T15:26:31Z
2020-06-03T15:26:31Z
2015-04-01
Genes Dev .2015 ;29(7):690-5.
10.1101/gad.256958.114
1549-5477
Genes & development
25838540
http://hdl.handle.net/20.500.12105/10264
In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile site expression and alleviates the severity of a progeroid disease by increasing RNR activity.
eng
Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.
journal article
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IncreasedRrm2genedosage_2015.pdf
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IncreasedRrm2genedosage_2015.pdf.txt
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