Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination

Abstract

In late mitosis and G1, Mcm2-7 are assembled onto replication origins to “license” them for initiation. At other times licensing is inhibited by cyclin dependent kinases (CDKs) and geminin, thus ensuring that origins fire only once per cell cycle. We show here that, paradoxically, CDKs are also required to inactivate geminin and activate the licensing system. On exit from metaphase in Xenopus egg extracts, CDK-dependent activation of the Anaphase Promoting Complex (APC/C) results in the polyubiquitination of geminin. This ubiquitination triggers geminin inactivation without requiring ubiquitin-dependent proteolysis, and is essential for replication origins to become licensed