Figure 8.

Model for re-replication control in the early Xenopus embryo. A small region of chromatin surrounding a single replication origin is shown. During metaphase, geminin is active and binds Cdt1, keeping it inactive. An excess of geminin over Cdt1 ensures complete Cdt1 inhibition. Cdk1 plays a subsidiary role by reducing the affinity of ORC and Cdc6 for the origin. On exit into anaphase,Cdk1-dependent APC/C activation occurs. The APC/C polyubiquitinates geminin, a significant proportion of which is deubiquitinated without being degraded, leaving it unable to inhibit Cdt1. Combined with the loss of Cdk1 activity during anaphase, this rapidly activates the licensing system and Mcm2–7 are loaded onto origins, displacing Cdc6. In early interphase (G1/S), chromosomal DNA is assembled into a nucleus. Geminin is imported into the nucleus and is re-activated, being recruited to chromatin with Cdt1. In addition, Cdt1 is degraded during early interphase. During S phase, initiation takes place at licensed origins, resulting in displacement of Mcm2–7 from origins, which allows Cdc6 to rebind ORC. Because of the presence of active geminin and the lack of Cdt1, replicated origins cannot be re-licensed and so DNA is not re-replicated.