Geminin (EM6) Mouse mAb #79148

The initiation of DNA replication in mammalian cells is a highly coordinated process that ensures duplication of the genome only once per cell division cycle. Origins of replication are dispersed throughout the genome and their activities are regulated via the sequential binding of pre-replication and replication factors. The origin recognition complex (ORC) is thought to be bound to chromatin throughout the cell cycle (1,2). The pre-replication complex (pre-RC) forms in late mitosis/early G1 phase beginning with the binding of CDT1 and cdc6 to the origin, which allows binding of the heterohexameric MCM2-7 complex. Once this complex is formed, the origin is “licensed” for initiation of DNA replication. In order to ensure that replication occurs only once per cell cycle, geminin binds to and inhibits CDT1 during the S, G2, and M phases. This prevents the recruitment of the MCM complex to the origins of replication, which blocks the premature reformation of the pre-RC. At the metaphase/anaphase transition, geminin is degraded by the anaphase-promoting complex (APC) allowing for the formation of a new pre-RC (3,4).