Miotic regulation of chromosome partitioning

 Simonetta PIATTI

 CRBM - UMR 5237

 1919, route de Mende, 34293 Montpellier

Phone: +33 4 34 35 95 46

Email: simonetta.piatti@crbm.cnrs.fr

Website

During cell division, chromosomes are faithfully duplicated and segregated, so that one copy of each chromosome can be inherited by the two daughter cells, which must carry identical genetic information. The fidelity of chromosome transmission has important medical implications. For example, aberrant chromosome numbers in eggs or sperms generate embryos that either undergo spontaneous miscarriage or display severe pathologies, such as the Down syndrome. Inaccurate genome partitioning during any of the millions of the cell divisions taking place in our body can lead to tumour development.

Our laboratory studies the surveillance mechanisms acting during mitosis to ensure proper genome partitioning, using the budding yeast Saccharomyces cerevisiae as a model organism. In particular, we are focusing on two aspects of mitosis that are crucial to prevent aneuploidies: a) how faithful chromosome segregation is overseen by the spindle assembly checkpoint (SAC) that monitors the correct attachment of chromosomes to the mitotic spindle; b) how mitotic exit and cytokinesis are regulated to preserve genome stability.

Keywords: cell cycle; cytokinesis; checkpoints; mitotic exit

Main publications

• Severin, F., Hyman, A.A. and Piatti, S. (2001). Correct spindle elongation at the metaphase/anaphase transition is an APC-dependent event in budding yeast. J. Cell Biol., 155: 711-717.
• Fraschini, R., Beretta, A., Sironi, L., Musacchio, A., Lucchini, G. and Piatti, S. (2001). Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores. EMBO J., 20: 6648-6659.
• Chiroli, E., Fraschini, R., Beretta, A., Tonelli, M, Lucchini, G. and Piatti, S. (2003). Budding yeast PAK kinases regulate mitotic exit by two independent mechanisms. J. Cell Biol. 160:857-874.
• Fraschini, R., Bilotta, D., Lucchini, G. and Piatti, S. (2004). Functional characterization of Dma1 and Dma2, the budding yeast homologues of Schizosaccharomyces pombe Dma1 and human Chfr. Mol. Biol. Cell 15:3796-3810.
• Fraschini, R., D'Ambrosio, C., Venturetti, M. Lucchini, G. and Piatti, S. (2006). Disappearance of the budding yeast Bub2/Bfa1 complex from the mother-bound spindle pole contributes to mitotic exit. J. Cell Biol. 172:335-346.
• Mapelli, M., Filipp, F., Rancati, G., Massimiliano, L., Nezi, L., Hagan, R., Sorger, P.K., Confalonieri, S., Piatti, S., Sattler, M. and Musacchio, A. (2006). Determinants of conformational dimerization of Mad2 and its inhibition by p31COMET. EMBO J., 25:1273-1284.
• Nezi, L., Rancati, G., De Antoni, A., Pasqualato, S., Piatti, S.* and Musacchio, A.* (2006). Accumulation of Mad2/Cdc20 complex during spindle checkpoint activation requires binding of open and closed conformers of Mad2 in Saccharomyces cerevisiae. J. Cell Biol., 174:39-51. *: corresponding authors.
• Chiroli, E., Rossio, V., Lucchini, G. and Piatti, S. (2007). The budding yeast PP2ACdc55 protein phosphatase prevents the onset of anaphase in response to morphogenetic defects. J. Cell Biol., 177:599-611.
• Chiroli E., Rancati, G., Catusi, I., Lucchini, G. and Piatti, S. (2009). Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. Mol. Biol. Cell 20:2626-37.
• Rossio, V., Galati, E., Ferrari, M., Pellicioli, A., Sutani, T., Shirahige, K., Lucchini, G. and Piatti, S. (2010). The RSC chromatin remodeling complex influences mitotic exit and adaptation to the spindle assembly checkpoint by controlling the Cdc14 phosphatase. J. Cell Biol.,191: 981-997.