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.
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.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
Related Article
-
Emi1 ensures timely mitosis
- Mitch Leslie
J. Cell Biol. 2007 177: 370.
[Full Text]
[PDF]
This article has been cited by other articles:
-
Ostapenko, D., Burton, J. L., Wang, R., Solomon, M. J.
(2008). Pseudosubstrate Inhibition of the Anaphase-Promoting Complex by Acm1: Regulation by Proteolysis and Cdc28 Phosphorylation. Mol. Cell. Biol.
28: 4653-4664
[Abstract]
[Full Text]
-
Walker, A., Acquaviva, C., Matsusaka, T., Koop, L., Pines, J.
(2008). UbcH10 has a rate-limiting role in G1 phase but might not act in the spindle checkpoint or as part of an autonomous oscillator. J. Cell Sci.
121: 2319-2326
[Abstract]
[Full Text]
-
Zielke, N., Querings, S., Rottig, C., Lehner, C., Sprenger, F.
(2008). The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles. Genes Dev.
22: 1690-1703
[Abstract]
[Full Text]
-
Whitehurst, A. W., Ram, R., Shivakumar, L., Gao, B., Minna, J. D., White, M. A.
(2008). The RASSF1A Tumor Suppressor Restrains Anaphase-Promoting Complex/Cyclosome Activity during the G1/S Phase Transition To Promote Cell Cycle Progression in Human Epithelial Cells. Mol. Cell. Biol.
28: 3190-3197
[Abstract]
[Full Text]
-
Cuvier, O., Stanojcic, S., Lemaitre, J.-M., Mechali, M.
(2008). A topoisomerase II-dependent mechanism for resetting replicons at the S-M-phase transition. Genes Dev.
22: 860-865
[Abstract]
[Full Text]