The Basics of Chromosome Segregation

Abstract

During cell division, chromosomes carrying thousands of genes are correctly transmitted to daughter cells via a motile apparatus named the mitotic spindle (a schematic outline of the cell (division) cycle is shown in Fig. 2.1). In postreplicative (post S phase) cells, chromosomes comprise duplicated sister chromatids. In the cell cycle stage called mitotic metaphase, all sister chromatid pairs are aligned and bi-oriented to the spindle apparatus. In anaphase, all sister chromatids separate in concert and segregate oppositely along the anaphase spindle (towards the spindle poles/centrosomes) into the two daughter cells (Fig. 2.2). The once-in-a-cell-cycle occurrence of the chromosome-segregation process suggests that this event should be studied with respect to cell cycle control (reviewed in Morgan 2006). Our current understanding of chromosome segregation was greatly advanced by the discovery of cyclin-dependent protein kinases (CDKs; Doree and Hunt 2002). CDKs promote cell-cycle transitions and are the main engines of the cell cycle (Sanchez and Dynlacht 2005). Mitotic CDKs are inactivated when bound cyclin is degraded by the 26S proteasome through the ubiquitin pathway (Hershko 2005) thereby promoting the transition from metaphase to anaphase. Simultaneously, securin, a key inhibitor of separase, the enzyme whose action triggers chromosome segregation, is degraded by the same mechanism (Yanagida 2000, 2005; Fig. 2.1). Cell cycle control and chromosome segregation are temporally coordinated using the same destruction motif. In meiosis, the sexual reproduction cycle, there are two types of metaphase. In metaphase I, homologous chromosomes are associated, and in anaphase I they segregate without sister chromatid separation (Clarke and Orr-Weaver 2006).