TY - JOUR
T1 - Spindle dynamics model explains chromosome loss rates in yeast polyploid cells
AU - Jelenic, Ivan
AU - Selmecki, Anna
AU - Laan, Liedewij
AU - Pavin, Nenad
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Cell cycle regulation
KW - Chromosome loss
KW - Chromosome segregation
KW - Genome instability
KW - Polyploidy
KW - Spindle assembly
KW - Theoretical modeling
UR - http://resolver.tudelft.nl/uuid:00fd4557-459a-4f1c-8097-a8ff09b2ceba
UR - http://www.scopus.com/inward/record.url?scp=85051845779&partnerID=8YFLogxK
U2 - 10.3389/fgene.2018.00296
DO - 10.3389/fgene.2018.00296
M3 - Article
AN - SCOPUS:85051845779
SN - 1664-8021
VL - 9
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - AUG
M1 - 296
ER -