Force generation and resistance in human mitosis

Abstract

Since the first observations of chromosome segregation over 150 years ago, efforts to observe the forces that drive mitosis have evolved alongside advances in microscopy. The mitotic spindle acts as the major generator of force through the highly regulated polymerization and depolymerization of microtubules as well as associated motor proteins. Centromeric chromatin, along with associated proteins including cohesin and condensin, is organized to resist these forces and ensure accurate chromosome segregation. Microtubules and centromeric chromatin join at the kinetochore, a complex protein superstructure. Ongoing research into the forces generated at the kinetochore-microtubule interface has resulted in a range of estimates for forces necessary to separate chromosomes, from tens to hundreds of piconewtons. Still, the exact magnitude and regulation of these forces remain areas of continuing investigation. Determining the precise forces involved in chromosome segregation is hindered by limitations of current measurement techniques, but advances such as optical tweezers combined with fluorescence microscopy are promising for future research.

Keywords: Centromere; Chromosome; Mitosis; Spindle.

Fig. 1

Schematic illustrating the major structural components of the mitotic spindle

Fig. 2

Structural basis of microtubules illustrating A the tubulin dimer, B cylindrical structure of protofilaments, C protofilaments forming a microtubule, and D/E microtubule polymerization/depolymerization

Fig. 3

Composition and organization of human centromeres. A Schematic depiction of a human centromere (Aldrup-MacDonald and Sullivan ; McKinley and Cheeseman 2016). B Schematic depiction of yeast centromere (Lawrimore and Bloom 2022). C Formation of bottlebrush structure of human chromosomes (Gibcus et al. 2018). D Model of human centromere organization (Sacristan et al. 2024)