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Cell Cycle. 2004 Nov;3(11):1358-62. Epub 2004 Nov 10.

A model for CDK2 in maintaining genomic stability.

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  • 1Department of Discovery Research, DNAX Research, Incorporated, Palo Alto, California 94304, USA.


Abundant CDK2/cyclin A activity is present in human cancer cells, suggesting that rapid S phase CDK2 inhibition would be an effective anti-cancer approach. The dynamic change of chromatin-loading and -dissociation of MCM proteins requires S phase CDK2 activity. CDK2 inhibition during replication leads to increased MCM complex association with DNA and triggers rereplication. Overreplication-induced DSB and RPA-ssDNA intermediates activate ATM and ATR, resulting in a p53 response which selectively deletes cells with unresolved rereplication.

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