Introduction

During metaphase, chromosomes align in the centre of the cell. Kinetochores at the centre of the chromosome are able to attach to the spindles. But how do you control the separation of chromosomes during anaphase happening when there are chromosomes that are unattached to the spindles? You use the spindle assembly complex (SAC), but this requires an important complex called the mitotic checkpoint complex (MCC).

Spindle Assembly Complex (SAC)

During protometaphase in mitosis, the SAC delays chromosome separation [3] when spindles are unattached to the poles of chromatids. This is essential to maintain genomic stability of the cell.[3] The SAC stimulates the activation of the MCC, where it binds and inhibits the anaphase-promoting complex (APC/C) – an E3 ubiquitin ligase that initiates the segregation of chromosomes using ubiquitylation activity. [1] The MCC disrupts the recognition of APC/C substrates, securin and Cl2 that are necessary to initiate anaphase.

Mitotic Checkpoint Complex

MCC is a complex that is made up of SAC proteins: Mad2, Mad3 and Cdc20 (a co-activator protein of APC/C) along with the mitotic checkpoint protein, Bub3. Bub3 is omitted from the structure as it isn’t essential for fission yeast and BUBR1 only appears in human APC/C inhibition, however, both are shown in figure 1.

Figure 1. Assembly of the MCC and MCC mediated inhibition of APC/C.

Figure 1 shows the general assembly of the MCC, where closed state Mad2-Cdc20 and the BUBR1-BUB3 bind to inhibit the APC/C, however, the assembly can be disrupted by p31comet. This will be explained further in the Molecular Mechanism section.