A non-proteolytic function of separase links the onset of anaphase to mitotic exit

Uhlmann, F., Wernic, D., Poupart, M.-A., Koonin, E.V. & Nasmyth, K. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 103, 375–386 (2000).

Nasmyth, K. Segregating sister genomes: the molecular biology of chromosome separation. Science 297, 559–565 (2002).

Visintin, R., Hwang, E.S. & Amon, A. Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus. Nature 398, 818–823 (1999).

Shou, W. et al. Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell 97, 233–244 (1999).

Bardin, A.J. & Amon, A. MEN and SIN: what's the difference? Nature Rev. Mol. Cell Biol. 2, 1–12 (2001).

Tinker-Kulberg, R.L. & Morgan, D.O. Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage. Genes Dev. 13, 1936–1949 (1999).

Granot, D. & Snyder, M. Segregation of the nucleolus during mitosis in budding and fission yeast. Cell Motil. Cytoskeleton 20, 47–54 (1991).

Yeong, F.M., Lim, H.H., Wang, Y. & Surana, U. Early expressed Clb proteins allow accumulation of mitotic cyclin by inactivating proteolytic machinery during S phase. Mol. Cell. Biol. 21, 5071–5081 (2001).

Shirayama, M., Toth, A., Galova, M. & Nasmyth, K. APCCdc20 promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Nature 402, 203–207 (1999).

Yeong, F.M., Lim, H.H., Padmashree, C.G. & Surana, U. Exit from mitosis in budding yeast: Biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20. Mol. Cell 5, 501–511 (2000).

Stegmeier, F., Visintin, R. & Amon, A. Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell 108, 207–220 (2002).

Jaspersen, S.L., Charles, J.F., Tinker-Kulberg, R.L. & Morgan, D.O. A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae. Mol. Biol. Cell 9, 2803–2817 (1998).

Lee, S.E., Frenz, L.M., Wells, N.J., Johnson, A.L. & Johnston, L.H. Order of function of the budding yeast mitotic exit-network proteins Tem1, Cdc15, Mob1, Dbf2, and Cdc5. Curr. Biol. 11, 784–788 (2001).

Shou, W. et al. Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex. BMC Mol. Biol. 3, 3 (2002).

Yoshida, S. & Toh-e, A. Budding yeast Cdc5 phosphorylates Net1 and assists Cdc14 release from the nucleolus. Biochem. Biophys. Res. Commun. 294, 687–691 (2002).

Sullivan, M., Lehane, C. & Uhlmann, F. Orchestrating anaphase and mitotic exit: separase cleavage and localization of Slk19. Nature Cell Biol. 3, 771–777 (2001).

Baum, P., Yip, C., Goetsch, L. & Byers, B. A yeast gene essential for regulation of spindle pole duplication. Mol. Cell Biol. 8, 5386–5397 (1988).

Hornig, N.C.D., Knowles, P.P., McDonald, N.Q. & Uhlmann, F. The dual mechanism of separase regulation by securin. Curr. Biol. 12, 973–982 (2002).

Uhlmann, F., Lottspeich, F. & Nasmyth, K. Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature 400, 37–42 (1999).

Hu, F. et al. Regulation of the Bub2–Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell 107, 655–665 (2001).

Yoshida, S., Asakawa, K. & Toh-e, A. Mitotic exit network controls the localization of Cdc14 to the spindle pole body in Saccharomyces cerevisiae. Curr. Biol. 12, 944–950 (2002).

Cheng, L., Hunke, L. & Hardy, C.F.J. Cell cycle regulation of the Saccharomyces cerevisiae Polo-like kinase Cdc5p. Mol. Cell. Biol. 18, 7360–7370 (1998).

Juang, Y.-L. et al. APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle. Science 275, 1311–1314 (1997).

Cohen-Fix, O. & Koshland, D. Pds1p of budding yeast has dual roles: inhibition of anaphase initiation and regulation of mitotic exit. Genes Dev. 13, 1950–1959 (1999).

Bembenek, J. & Yu, H. Regulation of the anaphase-promoting complex by the dual secificity phosphatase human Cdc14a. J. Biol. Chem. 276, 48237–48242 (2001).

Kaiser, B.K., Zimmerman, Z.A., Charbonneau, H. & Jackson, P.K. Disruption of centrosome structure, chromosome segregation, and cytokinesis by misexpression of human Cdc14A phosphatase. Mol. Biol. Cell 13, 2289–2300 (2002).

Bardin, A.J., Visintin, R. & Amon, A. A mechanism for coupling exit from mitosis to partitioning of the nucleus. Cell 102, 21–31 (2000).

Pereira, G., Höfken, T., Grindlay, J., Manson, C. & Schiebel, E. The Bub2p spindle checkpoint links nuclear migration with mitotic exit. Mol. Cell 6, 1–10 (2000).

Knop, M. et al. Epitope tagging of yeast genes using a PCR-based strategy: more tags and improved practical routines. Yeast 15, 963–972 (1999).

Wach, A., Brachat, A., Pöhlmann, R. & Philippsen, P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10, 1793–1808 (1994).

Gietz, R.D. & Sugino, A. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base restriction sites. Gene 74, 527–534 (1988).

Kushnirov, V.V. Rapid and reliable protein extraction from yeast. Yeast 16, 857–860 (2000).

Aris, J.P. & Blobel, G. Identification and characterization of a yeast nucleolar protein that is similar to a rat liver nucleolar protein. J. Cell Biol. 107, 17–31 (1988).