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Department of Genetics


Cell polarity, spindle orientation and cell cycle progression in yeast

Cell cycle progression is controlled by fundamental mechanisms conserved between yeast and humans. Stage-specific events are driven by oscillatory activation of cyclin-dependent kinases (CDKs) and other core cell cycle regulators, while surveillance mechanisms known as Checkpoints monitor crucial steps to enforce orderly progression only after individual steps are successfully completed. Since the first checkpoint characterized in S. cerevisiae, the DNA damage checkpoint, this model system has contributed toward uncovering a variety of surveillance mechanisms faithfully conserved in humans. These mechanisms are critical to avert genetic instability and cancer.

S. cerevisiae divides asymmetrically into a larger mother and smaller daughter (the bud). In order to undertake this highly polarized cell division, an axis of cell polarity is established early in the cell cycle with the emergence of a new bud. As a result, two distinctive compartments are generated with a narrow constriction between them - the mother-bud neck. Thus, during mitosis the spindle must orient along this mother-bud axis to ensure the faithful partitioning of the replicated chromosomes across the bud neck.

Spindle orientation is under strict surveillance by the Spindle Position Checkpoint (SPOC) to ensure the coordination between chromosome partition and cell cycle progression out of mitosis. This checkpoint is based on molecular sensors located at the spindle poles that can read their position in the mother versus daughter compartment to generate signals that coordinate this spatial information with cell cycle progression. The SPOC is intrinsically linked to the establishment of cell polarity and regulates the progression of mitosis by controlling the Mitotic Exit Network, a signal transduction cascade that regulates the phosphatase Cdc14. I am using S. cerevisiae to study polarity establishment, its underlying mechanistic links to the SPOC and the integral control of cell cycle progression. Furthermore, I am also exploring related mechanisms for cell polarity control in the fission yeast S. pombe. To achieve an integral view, we exploit a variety of techniques ranging from live imaging to biochemistry and from high throughput genetics to molecular biology.

Control of spindle orientation is crucial for any system producing cells with different fates, as is the case in self-renewing stem cell divisions. Moreover, asymmetries built into the centrosome cycle of self-renewing stem cells have been effectively anticipated by studies in S. cerevisiae. Therefore, understanding the molecular basis of the SPOC in yeast will provide valuable insight into similar mechanisms in those and other asymmetric cell divisions. Finally, comparative studies in S. cerevisiae and S. pombe have been instrumental to achieve a universal view of cell cycle control mechanisms. Thus, exploring how these two models deploy conserved machineries to promote distinctive themes in cell polarity will contribute key lessons to understand general controls for cell shape and organization. 

Key publications

· M. Geymonat, Q. Peng, Z. Guo, Z. Yu, J. Unruh, S. Jaspersen and M. Segal (2020) Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase. eLife 9: e59222.

· M. Geymonat, A. Spanos and K. Rittinger (2017) In vitro analysis of Tem1 GTPase activity and regulation by the Bfa1/Bub2 GAP. Methods Mol Biol 1505:71-80.

· M. Geymonat and M. Segal (2017) Intrinsic and extrinsic determinants linking spindle pole fate, spindle polarity and asymmetric cell division in the budding yeast S. cerevisiae. Results Probl Cell Differ 61: 49-82.

· V. Graml, X. Studera, J. Lawson, A. Chessel, M. Geymonat, M. Bortfeld-Miller, L. Wagstaff, T. Walter, E. Piddini and R. Carazo Salas (2014) A genomic multi-process survey of the machineries that control and link cell shape, microtubules and cell cycle. Dev Cell 31: 227-239.

· M. Geymonat, A. Spanos, S. Jensen and S. Sedgwick (2010) Phosphorylation of Lte1 by Cdk prevents polarized growth during mitotic arrest in S. cerevisiae. J Cell Biol 191: 1097- 1112.

· M. Geymonat, A. Spanos, G. de Bettignies and S. Sedgwick (2009) Lte1 contributes to Bfa1 localization rather than stimulating nucleotide exchenge by Tem1. J Cell Biol 187: 497-511.

· M. Geymonat, A. Spanos and S. Sedgwick (2009) Production of mitotic regulators using an autoselection system for protein expression in budding yeast. Methods Mol Biol 545: 63-80.


Contact details

Dr Marco Geymonat

Department of Genetics,
University of Cambridge,
Downing Street,
Cambridge CB2 3EH,
United Kingdom


Tel.: +44 (0)1223 333[to be determined]

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Marco Geymonat publications on PubMed