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Background: p21^WAF1 is a potent inhibitor of the cell-cycle regulatory cyclin-dependent kinases (Cdks). It acts on Cdks in the G1 and S phases of the cell cycle, and also binds to proliferating cell nuclear antigen (PCNA), blocking DNA replication in vitro. Transcription of p21^WAF1 can be induced by the human tumour suppressor protein p53, suggesting that the action of p21^WAF1 may be important in cancer prevention. We have investigated the interaction between p21^WAF1 and PCNA using a genetic two-hybrid screen and with arrays of synthetic peptides derived from the p21^WAF1 protein sequence.

Results We have established that the carboxy-terminal region of p21^WAF1 interacts with PCNA in a yeast two-hybrid screen. Interaction with p21^WAF1 involves the central loop of PCNA, which connects the two domains of the PCNA monomer. The interaction was finely mapped using peptides derived from the entire …