Separation of Sister Chromatids

At the end of metaphase, the bi-oriented chromosomes align at the metaphase plate. During this phase, the cohesin protein ring-complexes hold the sister chromatids together at the centromere region and prevent them from being pulled apart.

Metaphase to anaphase progression is triggered by the cyclin-Cdk-induced phosphorylation of a multisubunit, ubiquitin ligase enzyme – the anaphase-promoting complex, also known as the cyclosome or APC/C. Phosphorylated APC/C binds to a protein, Cdc20, forming an active complex.

The active APC/C complex recognizes an inhibitory protein called securin that is bound to a protease enzyme called separase. Prior to this recognition, securin inhibits the activity of separase.

The active APC/C complex tags securin with the protein ubiquitin, targeting it for proteasomal degradation. Destruction of securin releases separase.

The cyclin-Cdk complex also negatively regulates unbound separase activity through inhibitory phosphorylation.

The active APC/C complex causes the ubiquitination of cyclins, targeting them for proteasomal degradation. The destruction of cyclin removes the enzymatic activity of cyclin-dependent kinases or Cdks.

Inactivation of Cdks allows phosphatase enzymes to dephosphorylate separase and prevents Cdk-mediated inhibitory re-phosphorylation of separase. Dephosphorylation allows the separase enzyme to cleave the cohesin ring-complex that holds sister chromatids together.

Cohesin cleavage results in the absolute loss of sister-chromatid cohesion, marking the transition from metaphase to anaphase. The loss of cohesion permits the sister chromatids to separate and move to opposite poles of the spindle.