Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/10264
Título
Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.
Autor(es)
Fecha de publicación
2015-04-01
Cita
Genes Dev .2015 ;29(7):690-5.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Chromosome Breakage | Animals | Cell Line | Cell Survival | Cells, Cultured | Chromosome Fragile Sites | Enzyme Activation | Fibroblasts | Gene Dosage | Humans | Longevity | Mice | Nucleosides | Protein-Serine-Threonine Kinases | Ribonucleoside Diphosphate Reductase | Survival Analysis
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DOI
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- IncreasedRrm2genedosage_2015.pdf
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