Abstract

Chromosome segregation—the partitioning of genetic material into two daughter cells—is one of the most crucial processes in cell division. In all Eukaryotes, chromosome segregation is driven by the spindle, a microtubule-based, self-organizing subcellular structure. Extensive research performed over the past 150 years has identified numerous commonalities and contrasts between spindles in different systems. In this review, we use simple coarse-grained models to organize and integrate previous studies of chromosome segregation. We discuss sites of force generation in spindles and fundamental mechanical principles that any understanding of chromosome segregation must be based upon. We argue that conserved sites of force generation may interact differently in different spindles, leading to distinct mechanical mechanisms of chromosome segregation. We suggest experiments to determine which mechanical mechanism is operative in a particular spindle under study. Finally, we propose that combining biophysical experiments, coarse-grained theories, and evolutionary genetics will be a productive approach to enhance our understanding of chromosome segregation in the future.

Highlights

  • Cell division—the physical splitting of a mother cell into two daughter cells—is a fundamental and ubiquitous biological process: in the human body, several million cells divide every second [1]

  • In the chromosome-linked models, chromatid motion is only one process, pushing from central spindle microtubules

  • It has recently been shown that when human tissue culture cell spindles and the first mitotic spindle in C. elegans are simultaneously engaged in anaphase A and anaphase B: (1) chromatids move at the same speed as central spindle microtubules; and (2) damaging the central spindle leads to the complete cessation of chromatid motion [50]

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Summary

Introduction

Cell division—the physical splitting of a mother cell into two daughter cells—is a fundamental and ubiquitous biological process: in the human body, several million cells divide every second [1]. Understanding the extent to which this is true will, require understanding the forces acting on chromosomes in different spindles In this manuscript, we argue that describing the spindle at a coarse-grained level provides a powerful means to address both commonalities and contrasts in the mechanics of chromosome motion in anaphase. We argue that describing the spindle at a coarse-grained level provides a powerful means to address both commonalities and contrasts in the mechanics of chromosome motion in anaphase Such an approach lets us emphasize cellular-scale processes, which is the natural level of description for the micron-scale movements of chromosomes that occur during anaphase. We argue that truly understanding the commonalities and contrasts in chromosome segregation in different spindles will require integrating such mechanistic models into an evolutionary framework

Force Generation in Anaphase Spindles
Kinetochores
The Central Spindle
Mechanics and Its Relevance to Anaphase Spindles
Force Balance
Mechanics of Speed Governors
Forces Are Local and Dependent on Relative Positions and Velocities
Implications for Forces from Kinetochores
Implications for Forces from the Astral Region
Implications for Forces from the Central Spindle
Mechanics of Chromosome Segregation
Four Mechanical Models of Anaphase
Model 1
Model 2
Model 3
Model 4
Mechanism of Chromosome Segregation in the Four Models of Anaphase
Additional Mechanical Models of Anaphase
Findings
Conclusions and Outlook
Full Text
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