The spindle position checkpoint in budding yeast: the motherly care of MEN

Mitotic exit and cytokinesis must be tightly coupled to nuclear division both in time and space in order to preserve genome stability and to ensure that daughter cells inherit the right set of chromosomes after cell division. This is achieved in budding yeast through control over a signal transduction cascade, the mitotic exit network (MEN), which is required for mitotic CDK inactivation in telophase and for cytokinesis. Current models of MEN activation emphasize on the bud as the place where most control is exerted. This review focuses on recent data that instead point to the mother cell as being the residence of key regulators of late mitotic events

The budding yeast PP2ACdc55 protein phosphatase prevents the onset of anaphase in response to morphogenetic defects

Faithful chromosome transmission requires establishment of sister chromatid cohesion during S phase, followed by its removal at anaphase onset. Sister chromatids are tethered together by cohesin, which is displaced from chromosomes through cleavage of its Mcd1 subunit by the separase protease. Separase is in turn inhibited, up to this moment, by securin. Budding yeast cells respond to morphogenetic defects by a transient arrest in G2 with high securin levels and unseparated chromatids. We show that neither securin elimination nor forced cohesin cleavage is sufficient for anaphase in these conditions, suggesting that other factors contribute to cohesion maintainance in G2. We find that the protein phosphatase PP2A bound to its regulatory subunit Cdc55 plays a key role in this process, uncovering a new function for PP2ACdc55 in controlling a noncanonical pathway of chromatid cohesion removal

Uncovering resistance to microtubule targeting drugs

Drugs that alter microtubule dynamics have been used for decades for treating different types of cancers. Such drugs arrest cell cycle progression in mitosis, and induce apoptosis. However, a fraction of cells manages to survive, escapes from the arrest and resumes proliferation. Understanding the strategies of these cells is important to uncover the early stages of emergence of resistance. To this aim, we performed laboratory evolution experiments in yeast and in mammalian cells when microtubule dynamics is impaired. Our results show that cells follow reproducible strategies to escape the effect of the drug. Via mutations, aneuplouidy and non genetics mechanisms they recover microtubule functionality and decrease the propensity to die.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202