The Lopez-Aviles Group focus on the study of mitotic exit and the involvement of protein phosphatases in this transition, using the fission yeast Schizosaccharomyces pombe as a model organism.
The fission yeast S. pombe. Photo: J.Berger/M.Langegger/S.Hauf.
Yeast has been extensively used as a eukaryotic model system in research. It is genetically amenable, allowing deletion of genes, creation of conditional alleles, and gene tagging. On the other hand, there is a wide conservation of the core components involved in cell cycle control, and due to the small size of their genome, yeast presents less redundancy than higher eukaryotes.
In particular, the fission yeast S. pombe has been instrumental in our current understanding of mitotic entry. For this reason, we believe that S. pombe will be also a useful tool for the analysis of the mechanisms governing mitotic exit.
Cell cycle transitions
The discovery of the cyclins and cyclin dependent kinases (Cdk) resulted in a completely new way of looking at cell cycle transitions in eukaryotes. Fluctuations in the activity of these complexes were thought to explain how cells transit from one phase of the cell cycle to the next; however, it has become clear that these transitions are more complex.
For instance, in terms of mitotic entry and exit it was believed that an increase in the activity of the CyclinB-Cdk1 complex was sufficient to trigger mitotic events, and hence, a drop in its activity would lead to exit from mitosis. This simple notion, however, failed to explain how cells achieve the abruptness required to make cell cycle transitions irreversible. In recent years the idea of regulated phosphatases has gained strength; activation of the kinase must occur at the same time as inactivation of the counteracting phosphatase in order to achieve an irreversible shift in the phosphorylation status within the cell and vice versa.
For Saccharomyces cerevisiae mitotic exit, the phosphatase in charge of dephosphorylating Cdk1 targets, Cdc14, has been widely studied. However, the phosphatase regulating mitotic exit in other eukaryotes remains unclear. Although recent studies in mouse and Xenopus point towards PP1 or PP2A, the picture is still incomplete. The use of S. pombe as a model for mitotic exit will shed light into the involvement of these different phosphatases in this cell cycle transition.