Emi1 is needed to couple DNA replication with mitosis but does not regulate activation of the mitotic APC/C.
Ubiquitin-mediated proteolysis is critical for the alternation between DNA replication and mitosis and for the key regulatory events in mitosis. The anaphase-promoting complex/cyclosome (APC/C) is a conserved ubiquitin ligase that has a fundamental role in regulating mitosis and the cell cycle in all eukaryotes. In vertebrate cells, early mitotic inhibitor 1 (Emi1) has been proposed as an important APC/C inhibitor whose destruction may trigger activation of the APC/C at mitosis. However, in this study, we show that the degradation of Emi1 is not required to activate the APC/C in mitosis. Instead, we uncover a key role for Emi1 in inhibiting the APC/C in interphase to stabilize the mitotic cyclins and geminin to promote mitosis and prevent rereplication. Thus, Emi1 plays a crucial role in the cell cycle to couple DNA replication with mitosis, and our results also question the current view that the APC/C has to be inactivated to allow DNA replication.
Di Fiore
Barbara
B
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, England, UK.
Pines
Jonathon
J
D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology*; D044783:F-Box Proteins / Q000378:metabolism*; D064248:Geminin; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D018797:Cell Cycle Proteins; D016213:Cyclins; D044783:F-Box Proteins; C498960:FBXO5 protein, human; C577995:GMNN protein, human; D064248:Geminin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome