Spindle dynamics model explains chromosome loss rates in yeast polyploid cells

Spindle dynamics model explains chromosome loss rates in yeast polyploid cells

Jelenic, Ivan (University of Zagreb)
Selmecki, Anna (Creighton University, Omaha NE)
Laan, L. (TU Delft BN/Liedewij Laan Lab; Kavli institute of nanoscience Delft)
Pavin, Nenad (University of Zagreb)

2018

Faithful chromosome segregation, driven by the mitotic spindle, is essential for organismal survival. Neopolyploid cells from diverse species exhibit a significant increase in mitotic errors relative to their diploid progenitors, resulting in chromosome nondisjunction. In the model system Saccharomyces cerevisiae, the rate of chromosome loss in haploid and diploid cells is measured to be one thousand times lower than the rate of loss in isogenic tetraploid cells. Currently it is unknown what constrains the number of chromosomes that can be segregated with high fidelity in an organism. Here we developed a simple mathematical model to study how different rates of chromosome loss in cells with different ploidy can arise from changes in (1) spindle dynamics and (2) a maximum duration of mitotic arrest, after which cells enter anaphase. We apply this model to S. cerevisiae to show that this model can explain the observed rates of chromosome loss in S. cerevisiae cells of different ploidy. Our model describes how small increases in spindle assembly time can result in dramatic differences in the rate of chromosomes loss between cells of increasing ploidy and predicts the maximum duration of mitotic arrest.

Cell cycle regulation
Chromosome loss
Chromosome segregation
Genome instability
Polyploidy
Spindle assembly
Theoretical modeling

http://resolver.tudelft.nl/uuid:00fd4557-459a-4f1c-8097-a8ff09b2ceba

https://doi.org/10.3389/fgene.2018.00296

1664-8021

Frontiers in Genetics, 9 (AUG)

Institutional Repository

journal article

© 2018 Ivan Jelenic, Anna Selmecki, L. Laan, Nenad Pavin