Mechanisms of chromosome behaviour during mitosis

Abstract

For over a century, scientists have strived to understand the mechanisms that govern the accurate segregation of chromosomes during mitosis. The most intriguing feature of this process, which is particularly prominent in higher eukaryotes, is the complex behaviour exhibited by the chromosomes. This behaviour is based on specific and highly regulated interactions between the chromosomes and spindle microtubules. Recent discoveries, enabled by high-resolution imaging combined with the various genetic, molecular, cell biological and chemical tools, support the idea that establishing and controlling the dynamic interaction between chromosomes and microtubules is a major factor in genomic fidelity.Mitosis is the shortest but most visually stunning phase of the cell cycle, particularly in metazoan cells, in which the mitotic apparatus and chromosomes can be followed directly by high-resolution microscopy. In these cells, the mitotic spindle -the macromolecular machine responsible for chromosome segregation -comprises over 800 proteins 1 . Structurally, the spindle is built from highly dynamic microtubules (BOX 1). Most of the less dynamic microtubule minus ends reside near the poles of the spindle, whereas the more dynamic plus ends extend towards the spindle equator and the cortex of the cell (FIG. 1). As a result, microtubules between the spindle poles are organized into an antiparallel array, and microtubules outside of the spindle body form two radial asters that converge on the spindle poles.

Merotelic attachments allow alignment and stabilization of chromatids in meiosis II oocytes

“…Importantly, we have found that also wild-type MII oocytes frequently display merotelic attachments at the metaphase stage, as well as lagging chromosomes at anaphase onset. This strongly suggests that merotelic attachments contribute significantly to chromosome mis-segregation in wild-type female germ cells, similar to what previously been documented for somatic cells during mitosis 10,11,27 . In conclusion, our results show that merotely contributes to aneuploidy in mammalian oocytes.…”

“…We found that chromosomes at the spindle equator displayed an amphitelic configuration (Fig. 1e), a geometric orientation promoted by opposing end-on microtubule attachments to the sister kinetochores of chromosomes [10][11][12] . Occasionally, one of the two sister kinetochores of chromosomes were bi-directionally attached to microtubules, suggesting also the presence of merotelic attachments ( Supplementary Fig.…”

Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules

“…2b). Lack of chromosome pulling/pushing forces by end-onattached microtubules to bi-oriented kinetochores 19 , which keeps chromosomes around the spindle equator, may explain the inefficiency of this partial and transient congression. It may also be explained by the reduction of microtubule density in the middle of the spindle, due to lack of microtubule stabilization by end-on attachment.…”

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

“…Chromosome movement toward the spindle equator is initiated immediately after nuclear envelope breakdown (NEB) in prometaphase and is known as chromosome congression. 1,2 Chromosome movements during congression are driven by 2 main mechanisms: microtubule polymerization/depolymerization-based motion 3 and motor-dependent transport along microtubules. [4][5][6] The latter is mainly achieved through the coordinated activities of cytoplasmic Dynein, CENP-E and chromokinesins.…”