Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17685
Título
A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging.
Autor(es)
Murga, Matilde CNIO | Bunting, Samuel | Montaña, Maria F | Soria, Rebeca | Mulero, Francisca CNIO | Cañamero, Marta | Lee, Youngsoo | McKinnon, Peter J | Nussenzweig, Andre | Fernandez-Capetillo, Oscar CNIO
Fecha de publicación
2009-08
Cita
Nat Genet . 2009;41(8):891-8.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Although DNA damage is considered a driving force for aging, the nature of the damage that arises endogenously remains unclear. Replicative stress, a source of endogenous DNA damage, is prevented primarily by the ATR kinase. We have developed a mouse model of Seckel syndrome characterized by a severe deficiency in ATR. Seckel mice show high levels of replicative stress during embryogenesis, when proliferation is widespread, but this is reduced to marginal amounts in postnatal life. In spite of this decrease, adult Seckel mice show accelerated aging, which is further aggravated in the absence of p53. Together, these results support a model whereby replicative stress, particularly in utero, contributes to the onset of aging in postnatal life, and this is balanced by the replicative stress-limiting role of the checkpoint proteins ATR and p53.
MESH
DNA Replication | Stress, Physiological | Abnormalities, Multiple | Aging | Alleles | Animals | Apoptosis | Ataxia Telangiectasia Mutated Proteins | Brain | Cell Cycle Proteins | DNA Damage | DNA Repair | DNA-Activated Protein Kinase | DNA-Binding Proteins | Disease Models, Animal | Embryo, Mammalian | Fibroblasts | Humans | Mice | Nuclear Proteins | Phenotype | Progeria | Protein Kinase Inhibitors | Protein Serine-Threonine Kinases | Syndrome | Tumor Suppressor Protein p53
Versión en línea
DOI
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