2026-08-05T13:04:45Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/102642024-11-29T14:19:10Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2015-04-01 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. 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 Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.