GEMININ, AN INHIBITOR OF DNA-REPLICATION, IS DEGRADED DURING MITOSIS

We describe a novel 25 kDa protein, geminin, which inhibits DNA replic ation and is degraded during the mitotic phase of the cell cycle. Gemi nin has a destruction box sequence and is ubiquitinated anaphase-promo ting complex (APC) in vitro. In synchronized HeLa cells, geminin is ab sent during G1 phase, accumulates during S, G2, and M phases, and disa ppears at the time of the metaphase-anaphase transition. Geminin inhib its DNA replication by preventing the incorporation of MCM complex int o prereplication complex (preRC). We propose that geminin inhibits DNA replication during S, G2, and M phases and that geminin destruction a t the metaphase-anaphase transition permits replication in the succeed ing cell cycle.