Meyer, R. E. | Search bioRxiv

bioRxiv2020

Mps1 promotes poleward chromosome movements in meiotic pro-metaphase

In prophase of meiosis I, homologous partner chromosomes pair and become connected by crossovers. Chiasmata, the connections formed between the partners enable the chromosome pair, called a bivalent, to attach as a single unit to the spindle. When the meiosis I spindle forms in prometaphase, most bivalents are associated with a single spindle pole and go through a series of oscillations on the spindle, attaching to and detaching from microtubules until the partners of the bivalent are bi-oriented, that is, attached to microtubules from opposite sides of the spindle, and prepared to be segregated at anaphase I. The conserved, kinetochore-associated kinase, Mps1, is essential for the bivalents to be pulled by microtubules across the spindle in prometaphase. Here we show that MPS1 is not required for kinetochores to attach microtubules but instead is necessary to trigger the migration of microtubule-attached kinetochores towards the poles. Our data support the model that Mps1 triggers depolymerization of microtubule ends once they attach to kinetochores in prometaphase. Thus, Mps1 acts at the kinetochore to co-ordinate the successful attachment of a microtubule and the triggering of microtubule depolymerization to move the chromosome.

cell biology↗

bioRxiv2020

Mps1 expression is critical for chromosome orientation and segregation in yeast with high ploidy

In aneuploid cancer cells, the chromosome segregation apparatus is sensitive to increased chromosome number. The conserved protein kinase, Mps1, is a critical actor of this machinery, orienting the chromosomes properly on the spindle. Abnormally high levels of this kinase have been found in tumors with elevated chromosome number. However, it remains unclear, mechanistically, if and how cells with higher ploidy become dependent upon increased Mps1 levels. To answer these questions, we explored Mps1 dependence in yeast cells with increased sets of chromosomes. We discovered that having more chromosomes affects the ability of cells to orient chromosomes properly. The cells with increased numbers of chromosomes are particularly sensitive to the reduction of Mps1 activity. In mps1 loss of function mutants, cells display an extended prometaphase with a longer spindle and a delay in orienting properly the chromosomes. Altogether, our results suggest that increased numbers of chromosomes render cells more dependent on Mps1 for orienting chromosomes on the spindle. The phenomenon described here may be relevant in understanding why hyperdiploid cancer cells become excessively reliant on high Mps1 expression for successful chromosome segregation. Author summaryMost cells in solid tumors usually carry far more chromosomes than normal cells. Losing or gaining chromosomes during cell division can lead to aneuploidy (an abnormal number of chromosomes), cancer, and other diseases. Mps1 is a master regulator of cell division that is critical to keep the correct number chromosomes in each daughter cell. This master regulator has been shown to target and affect the function of various actors involved in cell division. Abnormally high levels of this master regulator are found in tumors with elevated chromosome numbers. The high levels of this regulator appear to be protecting these tumor cells. To answer if and how cells with higher ploidy become so dependent of Mps1, we generated yeast cells with increased set of chromosomes. Here, we report that cells with elevated chromosome number are particularly sensitive to the reduction of Mps1 level. In cells with higher ploidy and reduced level of Mps1, the progression during cell division is delayed. In the mutant cells, their ability to properly orient and segregate their chromosomes on the spindle is greatly reduced.

cancer biology↗