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).