Abstract

The mitotic spindle segregates chromosomes into two daughter cells during cell division. This process relies on the precise regulation of forces acting on chromosomes as the cell progresses through mitosis. The forces in the spindle are difficult to directly measure using the available experimental techniques. Here, we review the ideas and recent advances of how forces can be determined from the spindle shape. By using these approaches, it has been shown that tension and compression coexist along a single kinetochore fiber, which are balanced by a bridging fiber between sister kinetochore fibers. An extension of this approach to three dimensions revealed that microtubule bundles have rich shapes, and extend not simply like meridians on the Earth’s surface but, rather, twisted in a helical manner. Such complex shapes are due to rotational forces, which, in addition to linear forces, act in the spindle and may be generated by motor proteins such as kinesin-5. These findings open new questions for future studies, to understand the mechanisms of rotational forces and reveal their biological roles in cells.

Highlights

  • Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; Department of Physics, Faculty of Science, University of Zagreb, Bijenička cesta 32, 10000 Zagreb, Croatia

  • This process relies on the precise regulation of forces acting on chromosomes as the cell progresses through mitosis

  • An extension of this approach to three dimensions revealed that microtubule bundles have rich shapes, and extend not like meridians on the Earth’s surface but, rather, twisted in a helical manner

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Summary

Forces in the Mitotic Spindle

The mitotic spindle is a fascinating micromachine based on microtubules and their associated proteins, which divide duplicated chromosomes between two nascent daughter cells (Figure 1A). Bottom: image of a spindle from the fission yeast Schizosaccharomyces pombe, CENP‐A‐GFP (magenta), with microtubules labeled with SiR‐tubulin (green). The image is expressing tubulin labeled with GFP (green), and the kinetochore protein Ndc80p labeled with reproduced with (magenta) permission from image of aof forces spindle yeast tdTomato [11]. Though it is difficult to directly measure forces by the available experimental techniques, severalcircles represent kinetochores, circles are centrosomes centrioles inside, and the shaded studies were able to green tackle this challenge. In examples of pioneering work, forces that the spindle exertsForces on a single chromosome in anaphase been measured using a flexible needle in the spindle are important have to drive chromosome movements, and glass to generate the shape of the spindle. Spindles in lower eukaryotes, such as yeasts, consist of a single microtubule

From Forces
Deformation a Slender
Linear and Rotational Forces That Shape the Spindle
Twisting
Rotational Forces Generated by Motor Proteins
Conclusions
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