Editing Anaphase-promoting complex (section)

== Metaphase to anaphase transition ==

As metaphase begins, the [[spindle checkpoint]] inhibits the APC/C until all sister-kinetochores are attached to opposite poles of the [[mitotic spindle]], a process known as chromosome biorientation.  When all kinetochores are properly attached, the spindle checkpoint is silenced and the APC/C can become active. M-Cdks phosphorylate subunits on the APC/C that promote binding to Cdc20.  Securin and M cyclins (cyclin A and cyclin B) are then targeted by APC/C<sup>Cdc20</sup> for degradation.  Once degraded, separin is released, cohesin is degraded and sister chromatids are prepared to move to their respective poles for anaphase.<ref name= "Morgan_2007" />

It is likely that, in animal cells, at least some of the activation of APC/C<sup>Cdc20</sup> occurs early in the cell cycle (prophase or prometaphase) based on the timing of the degradation of its substrates.  [[Cyclin A]] is degraded early in mitosis, supporting the theory, but [[cyclin B]] and securin are not degraded until metaphase.  The molecular basis of the delay is unknown, but is believed to involve the key to the correct timing of anaphase initiation.  In animal cells the spindle checkpoint system contributes to the delay if it needs to correct the bi-orientation of chromosomes.  Though how the spindle checkpoint system inhibits cyclin B and securin destruction while allowing cyclin A to be degraded is unknown.  The delay may also be explained by unknown interactions with regulators, localization and phosphorylation changes.<ref name= "Morgan_2007" />

This initiates a [[negative feedback]] loop.  While activation of APC/C<sup>Cdc20</sup> requires M-Cdk, the complex is also responsible for breaking the cyclin to deactivate M-CdK.  This means that APC/C<sup>Cdc20</sup> fosters its own deactivation.  It is possible that this negative feedback is the backbone of Cdk activity controlled by M and S cyclin concentration oscillations.<ref name= "Morgan_2007" />