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Plos Genetics : Cdk2 is Required for P53-independent G2, Volume 6

By Biggins, Sue

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Book Id: WPLBN0003929563
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Cdk2 is Required for P53-independent G2, Volume 6  
Author: Biggins, Sue
Volume: Volume 6
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection, PLoS Genetics
Historic
Publication Date:
Publisher: Plos

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Biggins, S. (n.d.). Plos Genetics : Cdk2 is Required for P53-independent G2, Volume 6. Retrieved from http://www.nationalpubliclibrary.com/


Description
Description : The activation of phase-specific cyclin-dependent kinases (Cdks) is associated with ordered cell cycle transitions. Among the mammalian Cdks, only Cdk1 is essential for somatic cell proliferation. Cdk1 can apparently substitute for Cdk2, Cdk4, and Cdk6, which are individually dispensable in mice. It is unclear if all functions of non-essential Cdks are fully redundant with Cdk1. Using a genetic approach, we show that Cdk2, the S-phase Cdk, uniquely controls the G2/M checkpoint that prevents cells with damaged DNA from initiating mitosis. CDK2-nullizygous human cells exposed to ionizing radiation failed to exclude Cdk1 from the nucleus and exhibited a marked defect in G2/M arrest that was unmasked by the disruption of P53. The DNA replication licensing protein Cdc6, which is normally stabilized by Cdk2, was physically associated with the checkpoint regulator ATR and was required for efficient ATR-Chk1-Cdc25A signaling. These findings demonstrate that Cdk2 maintains a balance of S-phase regulatory proteins and thereby coordinates subsequent p53-independent G2/M checkpoint activation.

 

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