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

Koenig, C., H. Maekawa and E. Schiebel (2010). Mutual regulation of cyclin dependent kinase and the mitotic exit network. J. Cell Biol., 188, 351-368.

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.

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.

Maekawa., H., C. Priest, J. Lechner, G. Pereira and E. Schiebel. (2007). The yeast centrosome translates the positional information of the anaphase spindle into a cell cycle signal. J. Cell. Biol., 179: 423-436.

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

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

Maekawa, H., and Schiebel, E. (2004). Cdk1-Clb4 controls the interaction of astral microtubule plus ends with sub-domains of the daughter cell cortex. Genes Development, 18:1709-1724. (see Abstract).

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

Tanaka, T.U. et al. (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).

Janke, C. et al. (2002). Four new subunits of the Dam1-Duo1 complex reveal novel functions in sister kinetochore biorientation. EMBO J., 21: 181-193 (see Abstract).

Pereira, G. et al. (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. et al. (2000). The Bub2p spindle checkpoint links nuclear migration with mitotic exit. Mol. Cell, 6: 1-10 (see Abstract).