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Published online May 7, 2007
doi:10.1083/jcb.200611166
The Journal of Cell Biology, Vol. 177, No. 3, 425-437
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Di Fiore et al.
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Article

Emi1 is needed to couple DNA replication with mitosis but does not regulate activation of the mitotic APC/C

Barbara Di Fiore1,2 and Jonathon Pines1,2

1 Wellcome Trust/Cancer Research UK Gurdon Institute and 2 Department of Zoology, University of Cambridge, Cambridge CB2 1QN, England, UK

Correspondence to Jonathon Pines: j.pines{at}gurdon.cam.ac.uk

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.

Abbreviations used in this paper: APC/C, anaphase-promoting complex/cyclosome; DIC, differential interference contrast; Emi1, early mitotic inhibitor 1; IRES, internal ribosome entry site; MCM, minichromosome maintenance; NEBD, nuclear envelope breakdown; Rca, regulator of cyclin A; RPE, retinal pigment epithelium.


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