Figure 6.

Functional model of the Cdt1/geminin licensing switch on chromatin. Free Cdt1 can license DNA replication origins, but its activity is not controlled and leads to rereplication and S-phase checkpoint activation. In contrast, the Cdt1–geminin A-complex licenses origins in a precisely controlled manner, without rereplication or checkpoint activation. After nuclear import renders free geminin competent to interact with Cdt1 (Hodgson et al, 2002), the active A-complex incorporates additional geminin forming the I-complex blocked in further licensing activity. Degradation of Cdt1 and geminin during S phase and mitosis resets the system for another cycle.