Anaphase is a brief but dynamic stage in the cell division cycle, following the alignment of genetic material during metaphase. This stage is defined by the physical separation of sister chromatids and their movement to opposite ends of the dividing cell. It is the definitive point where duplicated genetic information is accurately partitioned, ensuring each daughter cell receives a complete and identical set of chromosomes. This separation is achieved through coordinated molecular signaling and mechanical forces, representing an irreversible commitment to cellular division.
Molecular Signals Initiating Separation
The initiation of anaphase is tightly controlled by the Spindle Assembly Checkpoint (SAC). This checkpoint acts as a safeguard, ensuring the cell does not proceed until every chromosome is properly attached to the spindle apparatus at both kinetochores. The SAC monitors the tension generated by opposing forces pulling on the sister chromatids, which must be equally balanced. Until this tension is achieved, the SAC produces an inhibitory signal that prevents the next step in the cell cycle.
The signal to proceed is the silencing of the SAC, which occurs when all chromosomes are correctly positioned at the metaphase plate. This silencing permits the activation of the Anaphase Promoting Complex/Cyclosome (APC/C) with its co-activator, Cdc20. The activated APC/C acts as an E3 ubiquitin ligase, marking specific target proteins for destruction by the proteasome.
A primary target for the APC/C is securin, which acts as a molecular leash on the protease separase. Once securin is degraded, active separase is released. The active separase enzyme targets the cohesin protein rings holding the sister chromatids together. Cleavage of the cohesin rings simultaneously dissolves the physical connection, marking the beginning of anaphase.
Chromosome Movement and Segregation
The physical separation and movement of chromosomes is achieved through two distinct, simultaneous processes: Anaphase A and Anaphase B. Anaphase A involves the movement of chromosomes directly toward the spindle poles. This movement is driven by the shortening of the kinetochore microtubules, which are the fibers attached to the centromere region of each chromosome.
Kinetochore-associated motor proteins, such as minus-end directed dynein, facilitate this poleward travel by “walking” the chromosome along the microtubule track. The movement is coupled to the depolymerization of the microtubule fiber itself. This depolymerization primarily occurs at the plus end anchored at the kinetochore, a mechanism sometimes described as the kinetochore “eating” its own track.
As the centromere leads the way, the chromosome arms trail behind, giving the moving chromosomes their characteristic V-shape. This dynamic shortening ensures the genetic material is pulled cleanly toward opposite sides of the cell. Precise coordination between motor proteins and microtubule depolymerization is necessary to maintain attachment while generating the pulling force.
Simultaneously, Anaphase B drives the separation of the spindle poles, which effectively elongates the cell and provides additional separation distance. Anaphase B relies on motor proteins acting on the interpolar microtubules, which overlap in the center of the spindle. Plus-end directed motor proteins, particularly from the kinesin-5 family, are localized to this overlap zone.
These motors push the two sets of antiparallel interpolar microtubules past each other, generating an outward sliding force that lengthens the mitotic spindle. In some cell types, this elongation is assisted by dynein motors anchored at the cell cortex that pull on the astral microtubules. The combined forces of Anaphase A and Anaphase B ensure complete segregation of the genetic material.
The Transition to Telophase
Anaphase concludes once the segregated sets of chromosomes arrive at their respective spindle poles. The arrival of the chromosomes signals the cell to begin reversing the morphological changes of early mitosis. The condensed chromosomes begin to decondense, unwinding into the less compact chromatin structure necessary for gene expression.
Concurrently, the nuclear envelope begins to reassemble around each set of separated chromosomes. Fragments of the nuclear membrane, often derived from the endoplasmic reticulum, are recruited to the chromosome surface. These fragments fuse to form a continuous double membrane, creating two distinct, nascent nuclei.
The mitotic spindle apparatus, having fulfilled its function, begins to rapidly disassemble through microtubule depolymerization. This breakdown is triggered by the continued APC/C-mediated degradation of M-phase cyclins, which inactivates cyclin-dependent kinases. The inactivation of these kinases allows phosphatases to reverse the phosphorylation events that drove early mitosis.
Finally, signals generated during late anaphase and early telophase initiate the physical division of the cytoplasm, known as cytokinesis. This typically involves the formation of a contractile ring or a cell plate to ensure the cell cleaves into two independent daughter cells.