2026-07-21T07:35:37Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/72302024-11-29T14:50:16Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Muñoz, Sergio author Búa, Sabela author Rodriguez-Acebes, Sara author Megias Vazquez, Diego author Ortega Jimenez, Sagrario author de Martino, Alba author Mendez, Juan author 2017 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. Cell Rep. 2017 ;19(5):928-938. 10.1016/j.celrep.2017.04.032 2211-1247 22111247 Cell reports 28467906 http://hdl.handle.net/20.500.12105/7230 CDC6 CDT1 DNA replication Replication origin TIssue dysplasia In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias