A direct interaction between proliferating cell nuclear antigen (PCNA) andCdk2 targets PCNA-interacting proteins for phosphorylation

Proliferating cell nuclear antigen is best known as a DNA polymerase access ory protein but has more recently also been shown to have different functio ns in important cellular processes such as DNA replication, DNA repair, and cell cycle control. PCNA has been found in quaternary complexes with the c yclin kinase inhibitor p21 and several pairs of cyclin-dependent protein ki nases and their regulatory partner, the cyclins. Here we show a direct inte raction between PCNA and Cdk2. This interaction involves the regions of the PCNA trimer close to the C termini. We found that PCNA and Cdk2 form a com plex together with cyclin A. This ternary PCNA-Cdk2-cyclin A complex was ab le to phosphorylate the PCNA binding region of the large subunit of replica tion factor C as well as DNA ligase I. Furthermore, PCNA appears to be a co nnector between Cdk2 and DNA ligase I and to stimulate phosphorylation of D NA ligase I. Based on our results, we propose the model that PCNA brings Cd k2 to proteins involved in DNA replication and possibly might act as an "ad aptor" for Cdk2-cyclin A to PCNA-binding DNA replication proteins.