2026-07-21T07:35:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/72302024-11-29T14:50:16Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Muñoz, Sergio
author
Búa, Sabela
author
Rodriguez-Acebes, Sara
author
Megias Vazquez, Diego
author
Ortega Jimenez, Sagrario
author
de Martino, Alba
author
Mendez, Juan
funder
Ministerio de Ciencia y Competitividad (España)
2019-02-25T12:12:50Z
2019-02-25T12:12:50Z
2017
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
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.
eng
CDC6
CDT1
DNA replication
Replication origin
TIssue dysplasia
In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias
journal article
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URL
https://repisalud.isciii.es/bitstreams/f8fba6f2-3973-40fe-9dfa-4a1d743f869e/download
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In Vivo DNA Re-replication_2017.pdf
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In Vivo DNA Re-replication-2017-mmc1.pdf
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In Vivo DNA Re-replication_2017.pdf.txt
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https://repisalud.isciii.es/bitstreams/9c1d36d5-5346-45e1-81a6-d63cb1054447/download
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In Vivo DNA Re-replication-2017-mmc1.pdf.txt