Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/7230
Título
In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias
Autor(es)
Muñoz, Sergio | Búa, Sabela | Rodriguez-Acebes, Sara CNIO | Megias Vazquez, Diego CNIO | Ortega Jimenez, Sagrario CNIO | de Martino, Alba CNIO | Mendez, Juan CNIO
Fecha de publicación
2017
Cita
Cell Rep. 2017 ;19(5):928-938.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Mammalian DNA replication origins are "licensed" by the loading of DNA helicases, a reaction that is mediated by CDC6 and CDT1 proteins. After initiation of DNA synthesis, CDC6 and CDT1 are inhibited to prevent origin reactivation and DNA overreplication before cell division. CDC6 and CDT1 are highly expressed in many types of cancer cells, but the impact of their deregulated expression had not been investigated in vivo. Here, we have generated mice strains that allow the conditional overexpression of both proteins. Adult mice were unharmed by the individual overexpression of either CDC6 or CDT1, but their combined deregulation led to DNA re-replication in progenitor cells and lethal tissue dysplasias. This study offers mechanistic insights into the necessary cooperation between CDC6 and CDT1 for facilitation of origin reactivation and describes the physiological consequences of DNA overreplication.
Palabras clave
MESH
Animals | Cell Cycle Proteins | DNA-Binding Proteins | Diarrhea, Infantile | Female | Intestinal Mucosa | Malabsorption Syndromes | Male | Mice | Nuclear Proteins | Transgenes | DNA Replication
Versión en línea
DOI
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