Equal chromosome segregation during mitosis is maintained by the separation of sister chromatids in a controlled manner. The mechanism by which chromosomes dissociate at anaphase has been solved elegantly both in yeast and mammalian cells by Uhlmann et al. [
30] and Waizenegger et al. [
31], respectively. The securin plays an important role in maintaining sister chromatids together until the onset of anaphase. The two sister chromatids are held together by a multisubunit cohesion complex [
32]. The Smc1p, Smc3p, and sister chromatid cohesion (Scc)1p are members of the SMC family of putative ATPase proteins that are associated with chromosomes to exert a cohesive force that opposes microtubule-induced chromosome splitting [
32]. Scc1p binds to chromosomes during S phase and dissociates at the onset of anaphase by a protein called separin. The premature activation of separin is prevented by the binding of securin, which is activated by the degradation of securin by anaphase-promoting complex (APC) during anaphase [
33]. The APC, also called cyclosome [
34], is an ubiquitin ligase (E3) complex consisting of different subunits that ubiquitinate mitotic cyclins [
34], securin [
10,
35‐
37], and other cell cycle proteins [
38,
39]. The APC/C is activated by WD repeat proteins in a cell cycle-specific manner and the activation pattern of the APC/C is remarkably conserved from yeast to human. The APC/C is activated at metaphase and persists until the G
1 to S-phase transition [
40,
41]. The APC/C is activated initially by fizzy (fzy), a
Drosophila homologue of p55
CDC in rat and human, during the metaphase transition. Fzy is degraded later in mitosis (G
1 and G
0) and is replaced by the fzy-related (fzr) proteins that activate APC/C [
42]. The fzy-mediated APC/C activity is required for the degradation of securin during the onset of anaphase, while fzr-mediated APC/C activity is essential for the degradation of mitotic cyclins, fzy, and other substrates [
38,
39].