Spindle Dynamics Model Explains Chromosome Loss Rates in Yeast Polyploid Cells

Jelenić, Ivan and Selmecki, Anna and Laan, Liedewij and Pavin, Nenad (2018) Spindle Dynamics Model Explains Chromosome Loss Rates in Yeast Polyploid Cells. Frontiers in Genetics, 9. Art. 296. ISSN 1664-8021

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Abstract

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.

Item Type: Article
Keywords: polyploidy, spindle assembly, chromosome loss, chromosome segregation, cell cycle regulation, theoretical modeling, genome instability
Date: 2018
Subjects: NATURAL SCIENCES > Physics > Biophysics and Medical Physics
Additional Information: Copyright © 2018 Jelenić, Selmecki, Laan and Pavin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Received: 02 March 2018. Accepted: 13 July 2018. Published: 06 August 2018.
Divisions: Faculty of Science > Department of Physics
Publisher: Frontiers Media
Depositing User: Gordana Stubičan Ladešić
Date Deposited: 31 Aug 2018 07:47
Last Modified: 31 Aug 2018 07:47
URI: http://digre.pmf.unizg.hr/id/eprint/5842

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