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PubMed · 15492512

A model for CDK2 in maintaining genomic stability.

Yonghong Zhu
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Abstract

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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Antineoplastic AgentsApoptosisCell Line, TumorCyclin ACyclin-Dependent Kinase 2DNADNA DamageDNA ReplicationGenomic InstabilityHumansModels, GeneticProtein Kinase InhibitorsRNA InterferenceS PhaseTumor Suppressor Protein p53Journal Article

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Yonghong Zhu. 2004-11-10. A model for CDK2 in maintaining genomic stability.. https://doi.org/10.4161/cc.3.11.1226

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