During mitosis, the duplicated chromosomes are segregated to opposite poles by the mitotic spindle. The mitotic spindle consists of the two spindle poles each containing one centrosome or spindle pole body (SPB) and microtubules that connect the poles with specialized regions of the chromosome, the kinetochores. Chromosome segregation in mitosis is a temporally and spatially well-defined process. In metaphase, the condensed chromosomes are aligned near the spindle equator (metaphase plate). The chromosomes are then moved towards the poles as the spindle elongates in anaphase. Finally, the cell divides near the spindle equator in a step known as cytokinesis and exits into a new cell cycle. Regulatory networks, so called checkpoints, coordinate the timing of events in mitosis. The spindle checkpoint inhibits anaphase until all of the kinetochores are attached to microtubules. The mitotic exit network (MEN) makes cytokinesis and mitotic exit dependent upon chromosome segregation in anaphase.

Using budding yeast, chicken DT40 and mammalian cells, we are focusing on following topics:

• the duplication and maturation of the centrosome, in yeast and mammalian cells
• the function of the Hippo pathway at mammalian centrosomes
• the function of the conserved phosphatase Cdc14 in yeast, DT40 and mammalian cells
• assembly and regulation of the mitotic spindle
  
  

Questions are addressed using a broad range of methods including yeast genetics, biochemistry, electron microscopy, live cell imaging, FRET, molecular biology.

Selected publications

Mardin, B.R., M. Isokane, M.R. Cosenza, A. Krämer, J. Ellenberg, A.M. Fr, and E. Schiebel. (2013). EGF induced centrosome separation promotes mitotic progression and cell survival. Dev. Cell, 25:229-240 (see Abstract).

Erlemann, S., A. Neuner, L. Gombos, R. Gibeaux, C. Anthon, and E. Schiebel. (2012). An extended gamma-tubulin ring functions as a stable platform in microtubule nucleation. J. Cell Biol., 197:59-74 (see Abstract).

Roostalu, J., C. Hentrich, P. Bieling, I.A. Telley, E. Schiebel* and T. Surrey*. (2011). Directional switching of the kinesin Cin8 through motor coupling. Science, 332:94-99 (see Abstract). * Co-corresponding authors.

Mardin, B.R., C. Lange, J.E. Baxter, T. Hardy, S.R. Scholz, A.M. Fry and E. Schiebel. (2010). Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nature Cell Biol., 12:1166-1176 (see Abstract).

Khmelinskii, A., P.J. Keller, H. Lorenz, E. Schiebel* and M. Knop*. (2010). Segregation of yeast nuclear pores. Nature, 466(7305):E1 (see Abstract). * Co-corresponding authors.

Mocciaro, A., E. Berdougo, K. Zeng, E. Black, P. Vagnarelli, W. Earnshaw, D. Gillespie, P. Jallepalli* and E. Schiebel*. (2010). Cells deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired for DNA repair. J. Cell Biol., 189:631-639 (see Abstract). * Co-corresponding authors.

Khmelinskii, A., J. Roostalu, H. Roque, C. Antony and E. Schiebel. (2009). Phosphorylation-dependent protein interactions at the spindle midzone mediate cell cycle regulation of spindle elongation. Dev. Cell, 17:244-256 (see Abstract).

Sezen, B., M. Seedorf and E. Schiebel. (2009). The SESA network links duplication of the yeast centrosome with the protein translation machinery. Genes Development, 23:1559-1570 (see Abstract).

Khmelinskii, A. , C. Lawrence, J. Roostalu and E. Schiebel. (2007). Cdc14-regulated midzone assembly controls anaphase B. J. Cell Biol., 177: 981-993 (see Abstract).

Pereira, G.* and E. Schiebel*. (2005). Kin4 kinase delays mitotic exit in response to spindle alignment defects. Mol. Cell, 19: 209-221 (see Abstract). * Co-corresponding authors.

Pereira, G.* and E. Schiebel*. (2003). Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science, 302: 2120-2124 (see Abstract). * Co-corresponding authors.

Tanaka, T.U., N. Rachidi, C. Janke, G. Pereira, M. Galova, E. Schiebel, M.J.R. Stark and K. Nasmyth. (2002). Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell, 108: 317-329. (see Abstract).

Pereira, G., T.U. Tanaka, K. Nasmyth and E. Schiebel (2001). Modes of spindle pole body inheritance and segregation of the Bfa1p/Bub2p checkpoint protein complex. EMBO J., 20: 6359-6370 (see Abstract).

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