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APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit

Abstract

Cyclin degradation is central to regulation of the cell cycle. Mitotic exit was proposed to require degradation of the S phase cyclin Clb5 by the anaphase-promoting complex1,2 activated by Cdc20 (APCCdc20)3. Furthermore, Clb5 degradation was thought to be necessary for effective dephosphorylation and activation of the APC regulatory subunit Cdh1 (also known as Hct1) and the cyclin-dependent kinase inhibitor Sic1 by the phosphatase Cdc14, allowing mitotic kinase inactivation and mitotic exit3,4,5,6,7. Here we show, however, that spindle disassembly and cell division occur without significant APCCdc20-mediated Clb5 degradation, as well as in the absence of both Cdh1 and Sic1. We find instead that destruction-box-dependent degradation of the mitotic cyclin Clb2 is essential for mitotic exit. APCCdc20 may be required for an essential early phase of Clb2 degradation, and this phase may be sufficient for most aspects of mitotic exit. Cdh1 and Sic1 may be required for further inactivation of Clb2–Cdk1, regulating cell size and the length of G1.

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Figure 1: Clb5 degradation is Cdc20 and D-box dependent, but Clb5Δdb does not block mitotic exit.
Figure 2: CLB2Δdb but not CLB5Δdb sic1Δ or cdh1Δ sic1Δ blocks mitotic exit.
Figure 3: Kinetics of mitotic exit.
Figure 4: D-box-dependent Clb2 proteolysis depends on Cdc20 and Cdh1, and KEN-dependent proteolysis only on Cdh1.
Figure 5: Model of mitotic control.

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Acknowledgements

We thank A. Amon, K. Nasmyth, M. Tyers, E. Schwob, W. Seufert and M. Shirayama for reagents and A. Amon, K. Nasmyth, J. Roberts and M. Tyers for useful discussions and critical comments on the manuscript. We also thank C. Li and A. Doty for technical assistance and J. Schmoranzer for help with some micrographs. This work was supported by a grant from Deutsche Krebshilfe to R.W. and a PHS grant to F.C.

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Correspondence to Frederick R. Cross.

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Wäsch, R., Cross, F. APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit. Nature 418, 556–562 (2002). https://doi.org/10.1038/nature00856

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