Page "Spindle checkpoint" Paragraph 34

Several mechanisms exist to deactivate the SAC after correct bi-orientation of sister chromatids.

Upon microtubule-kinetochore attachment, a mechanism of stripping via a dynein-dynein motor complex transports spindle checkpoint proteins away from the kinetochores.

The stripped proteins, which include MAD1, MAD2, MPS1, and CENP-F, are then redistributed to the spindle poles.

The stripping process is highly dependent on undamaged microtubule structure as well as dynein motility along microtubules.

As well as functioning as a regulator of the C-MAD2 positive feedback loop, p31 < sup > comet </ sup > also may act as a deactivator of the SAC.

Unattached kinetochores temporarily inactivate p31 < sup > comet </ sup >, but attachment reactivates the protein and inhibits MAD2 activation, possibly by inhibitory phosphorylation.

Another possible mechanism of SAC inactivation results from energy-dependent dissociation of the MAD2-CDC20 complex through non-degradative ubiquitylation of CDC20.

Conversely, the de-ubiquitylating enzyme protectin is required to maintain the SAC.

Thus, unattached kinetochores maintain the checkpoint by continuously recreating the MAD2-CDC20 subcomplex from its components.

The SAC may also be deativated by APC activation induced proteolysis.

Since the SAC is not reactivated by the loss of sister-chromatid cohesion during anaphase, the proteolysis of cyclin B and inactivation of the CDK1-cyclin-B kinase also inhibits SAC activity.

Degradation of MPS1 during anaphase prevents the reactivation of SAC after removal of sister-chromatid cohesion.

After checkpoint deactivation and during the normal anaphase of the cell cycle, the anaphase promoting complex is activated through decreasing MCC activity.

When this happens the enzyme complex polyubiquitinates the anaphase inhibitor securin.

The ubiquitination and destruction of securin at the end of metaphase releases the active protease called separase.

Separase cleaves the cohesion molecules that hold the sister chromatids together to activate anaphase.