Involvement of the interaction between p21 and proliferating cell nuclear antigen for the maintenance of G2/M arrest after DNA damage.

Although a major effect of p21, a cyclin-dependent kinase inhibitor, is considered to be exerted during G(1) phase of the cell cycle, p21 gene knock-out studies suggested its involvement in G(2)/M checkpoint as well. Here we demonstrate evidence that p21 is required for the cell cycle arrest at G(2) upon ...
DNA damage. We found that expression of wild-type p21 (p21(WT)), not mutant p21 (p21(PCNA-)) lacking the interaction with proliferating cell nuclear antigen (PCNA), caused G(2) cell cycle arrest in p53-deficient DLD1 colon cancer cell line after the DNA damage by treatment with cis-diamminedichloroplatinum (II). We also found that p21(WT) was associated with Cdc2/cyclin B1 together with PCNA. Furthermore, coimmunoprecipitation experiments revealed that PCNA interacted with Cdc25C at the G(2)/M transition, and this interaction was abolished when p21(WT) was expressed presumably due to the competition between p21(WT) and Cdc25C in the binding to PCNA. These findings suggest that p21 plays a regulatory role in the maintenance of cell cycle arrest at G(2) by blocking the interaction of Cdc25C with PCNA.
Mesh Terms:
Amino Acid Sequence, Antineoplastic Agents, Binding, Competitive, Blotting, Western, Cisplatin, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, DNA Damage, Flow Cytometry, G2 Phase, Genes, p53, Humans, Mitosis, Molecular Sequence Data, Mutation, Phosphorylation, Precipitin Tests, Proliferating Cell Nuclear Antigen, Protein Binding, Time Factors, Tumor Cells, Cultured
J. Biol. Chem.
Date: Nov. 16, 2001
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