metaphasetoanaphase

The metaphase-to-anaphase transition is a key regulatory stage in mitosis during which sister chromatids separate and are directed to opposite poles of the cell. This transition follows successful alignment of chromosomes at the metaphase plate and proper bi-orientation of kinetochores.

Control of the transition relies on the spindle assembly checkpoint (SAC), which monitors kinetochore attachments and the tension generated between sister kinetochores. If any chromosome is unattached or improperly attached, the SAC inhibits the anaphase-promoting complex/cyclosome (APC/C) activated by its co-activator Cdc20, delaying anaphase onset. Once all chromosomes achieve proper attachment and tension, the SAC is satisfied and APC/C-Cdc20 becomes active.

APC/C-Cdc20 targets securin and cyclin B for ubiquitin-mediated degradation. Degradation of securin releases separase, a protease that cleaves cohesin complexes holding sister chromatids together, enabling chromatid separation. Degradation of cyclin B lowers CDK1 activity, promoting mitotic exit and progression into anaphase.

In anaphase, chromosome movement occurs in two coordinated phases. Anaphase A involves shortening of kinetochore microtubules and poleward movement of chromatids toward the poles. Anaphase B involves poleward spindle elongation driven by motor proteins and sliding microtubules, further separating the poles. These processes ensure accurate chromosome segregation and set the stage for telophase and cytokinesis.

Errors in the metaphase-to-anaphase transition, such as merotelic attachments or lagging chromosomes, can lead to aneuploidy. Cellular safeguards, including tension sensing and error correction mechanisms, strive to prevent such missegregation.