Cyclin A-Cdk2 (CCNA:CDK2) prevents unscheduled APC reactivation during S phase by binding and subsequently phosphorylating FZR1 (Cdh1). Phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits the APC/C (Sorensen et al. 2001). DNA damage activates ATM kinase, resulting in TP53-mediated induction of CDKN1A (p21) expression. CDKN1A binds CCNA:CDK2 complex and prevents its association with Cdh1 (Takahashi et al. 2012).
Takahashi, A, Imai, Y, Yamakoshi, K, Kuninaka, S, Ohtani, N, Yoshimoto, S, Hori, S, Tachibana, M, Anderton, E, Takeuchi, T, Shinkai, Y, Peters, G, Saya, H, Hara, E
Sorensen, CS, Lukas, C, Kramer, ER, Peters, JM, Lukas, J
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