Anaphase AEdit
Anaphase A is the initial phase of chromosome segregation in mitosis, during which sister chromatids are pulled away from each other toward opposite spindle poles. This movement occurs after the chromosomes have properly aligned at the cell’s equator in metaphase and before the spindle stretches further during anaphase B. In most cells, anaphase A is driven primarily by changes in the microtubules that connect chromosomes to the poles, with motor proteins and microtubule dynamics generating the pulling forces necessary for rapid separation. The process is tightly coordinated with the destruction of specific cell-cycle inhibitors, ensuring that chromosome separation happens only when the genome is ready to be divided.
The distinction between anaphase A and anaphase B is important: anaphase A focuses on the movement of chromosomes toward the poles, largely due to kinetochore microtubule dynamics, while anaphase B involves the elongation of the spindle itself as poles move farther apart. Both phases contribute to the overall distribution of genetic material to daughter cells, but the mechanistic emphasis of anaphase A is on the shortening and remodeling of kinetochore attachments rather than on spindle elongation alone.
Mechanism
Kinetochore dynamics and chromosome movement
Chromosomes are tethered to spindle poles by microtubules attached at kinetochores. In anaphase A, several coordinated processes drive poleward chromosome movement: - Depolymerization at kinetochores: Kinetochore-associated microtubules shorten as tubulin subunits are removed from the plus ends at the kinetochore, generating a pulling force that draws chromatids toward the poles. This “Pac-Man”–like mechanism is a classic description of how microtubule dynamics contribute to chromosome movement. - Poleward flux: Microtubule subunits can be lost from the minus ends near the poles, producing a flux of subunits toward the poles and contributing to chromosome locomotion along the spindle. - Motor proteins: Dynein and other motor proteins anchored at kinetochores or elsewhere on the spindle harness microtubule tracks to enhance or guide poleward movement, interacting with the changing lattice as microtubules shorten.
Cohesin removal and sister chromatid separation
Anaphase onset is governed by cell-cycle regulators that ensure genetic material is prepared for separation. The Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase targets securin for destruction, releasing separase to cleave the cohesin complexes that hold sister chromatids together. Once cohesin at centromeres is removed, sister chromatids can separate and be pulled toward opposite poles by the mechanisms described above. Cohesin removal is a prerequisite for anaphase, and the precise choreography of cohesin cleavage helps ensure accurate chromosome segregation.
Variation across cell types
The relative contributions of kinetochore microtubule shortening, poleward microtubule flux, and motor activity differ among organisms, cell types, and even individual cells. In some systems, kinetochore depolymerization is the dominant driver of poleward movement, while in others substantial movement arises from microtubule flux or a combination of mechanisms. This variability is reflected in experimental observations that, for example, human somatic cells may rely on multiple concurrent processes to achieve efficient anaphase A, whereas other species may emphasize one mechanism more strongly.
Regulation and checkpoints
Anaphase A is tightly controlled to prevent premature chromosome separation or unequal distribution. Key regulatory elements include: - APC/C and its activator Cdc20: Trigger the metaphase-to-anaphase transition by tagging securin and other substrates for destruction, enabling separase activation and sister-chromatid separation. - Cohesin and its regulators: The cohesin complex holds chromatids together, with protection at centromeres (in some systems) by factors such as shugoshin until the appropriate stage of anaphase. - Kinases and phosphatases that modulate microtubule dynamics: Changes in microtubule stability and kinetochore-microtubule attachment strength are coordinated with cell-cycle progression to ensure robust chromosome movement.
Controversies and research fronts
Several debates persist about the precise mechanics of anaphase A, illustrating the richness of cell biology research: - Relative contributions of depolymerization versus microtubule flux: Some studies emphasize direct shortening of kinetochore microtubules as the main driver, while others show substantial, context-dependent contributions from poleward flux and lattice remodeling. The balance appears to vary by organism and cell type, leading to a nuanced, dual-mechanism view rather than a single universal model. - Role of motor proteins at kinetochores: The exact necessity and location of motor activity during anaphase A—whether dynein at kinetochores, dynein at spindle poles, or plus-end–directed motors in other locations—remains an active area of investigation, with differing results across model systems. - Integration with anaphase B: Although conceptually distinct, the two phases interact in time and space. Understanding how cells transition from the chromosome-directed movements of anaphase A to the spindle elongation of anaphase B continues to be refined as imaging and quantitative analyses improve.