Anaphase is the brief, irreversible moment in cell division when duplicated chromosomes are physically pulled apart, sending one complete set to each side of the cell. The entire process can be over in minutes, yet it determines whether each daughter cell inherits the right number of chromosomes. Errors here are not hypothetical edge cases; they are a leading source of the chromosome imbalances found in miscarriages, birth defects, and cancer. What makes anaphase so consequential is that once it starts, the cell is committed. There is no going back.
The Gate That Must Open First
Cells do not stumble into anaphase. A surveillance system called the spindle assembly checkpoint holds the cell in the preceding stage, metaphase, until every single chromosome is properly attached to the molecular machinery that will pull it apart. The checkpoint works by blocking the activity of a protein complex called the APC/C, which is the master switch for anaphase. Unattached chromosomes catalyze the assembly of an inhibitor, the mitotic checkpoint complex, that locks onto the APC/C and keeps it inactive. Even one unattached chromosome is enough to sustain this arrest.
The inhibitor itself has a clever design. It contains a protein called Cdc20, which also happens to be the very molecule the APC/C needs to become active. So while the checkpoint is engaged, Cdc20 is being sequestered into the inhibitory complex instead of activating the APC/C, creating a double lock on the system.
1PubMed Central. Spindle assembly checkpoint activation and silencing at kinetochoresOnly when every chromosome achieves stable, bipolar attachment to spindle fibers from opposite poles does the checkpoint fall silent. The inhibitory complex disassembles, Cdc20 is freed to activate the APC/C, and the cell crosses the threshold into anaphase. Research in fission yeast has shown that timely silencing of this checkpoint depends on additional factors that prevent the inhibitory complex from lingering too long on the APC/C. Without these factors, cells show delayed entry into anaphase and increased rates of chromosome errors.
2PubMed Central. Recovery from spindle checkpoint-mediated arrest requires a novel Dnt1-dependent APC/C activation mechanismThere are also more subtle forms of regulation. Structural modifications to the APC/C itself can weaken its grip on the inhibitory complex, providing another layer of control over exactly when the checkpoint releases. Biochemical work has demonstrated that one such modification reduces the stability of the APC/C-inhibitor interaction, helping to fine-tune the transition.
3Cell Reports. Structural basis of APC/C regulation by SUMOylationCutting the Molecular Glue
What actually holds sister chromosomes together before anaphase is a ring-shaped protein complex called cohesin, which physically embraces both sister chromatids like a molecular handcuff. The APC/C, once activated, triggers the destruction of a protein called securin. While securin exists, it keeps a powerful enzyme called separase locked in an inactive state. Destroy securin, and separase is unleashed.
4PubMed. Separase-mediated cleavage of cohesin at interphase is required for DNA repairSeparase then cuts a specific subunit of the cohesin ring. This cleavage is essential. Work in human cells confirmed that without separase-mediated cohesin cleavage, sister chromatids cannot separate and the cell cannot complete division.
5PubMed. Cohesin cleavage by separase required for anaphase and cytokinesis in human cellsThe logic is elegant in its simplicity: checkpoint holds APC/C inactive → chromosomes attach → checkpoint silences → APC/C activates → securin is destroyed → separase cuts cohesin → chromosomes fly apart. Each step depends absolutely on the one before it, creating a one-way cascade that commits the cell to division.
Two Phases of Chromosome Movement
Chromosome separation during anaphase actually involves two overlapping but mechanically distinct processes, traditionally called anaphase A and anaphase B. Understanding both is important because different cell types rely on them to different degrees, and failures in either can produce errors.
In anaphase A, chromosomes move toward the spindle poles. The fibers connecting each chromosome to its respective pole shorten, reeling the chromosomes inward. This shortening happens through two mechanisms working simultaneously. At the chromosome-facing end of each fiber, the fiber is actively chewed back, a process sometimes called the “Pacman” mechanism because the chromosome’s attachment point essentially eats its way along the shrinking fiber. At the pole-facing end, the fiber slides poleward and is disassembled there. In newt lung cells, detailed measurements showed that disassembly at the chromosome end accounted for roughly two-thirds of fiber shortening during anaphase A, while disassembly at the pole contributed about one-third.
6PubMed Central. Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A in newt lung cell mitosisThis balance is not universal. In frog egg extracts, the contribution flips: poleward sliding of fibers (called flux) accounts for nearly all of the chromosome-to-pole movement, with the rate of flux closely matching the rate of chromosome movement. In vertebrate somatic cells, by contrast, the Pacman mechanism at the chromosome attachment site dominates.
7PubMed Central. Anaphase A chromosome movement and poleward spindle microtubule flux occur at similar rates in Xenopus extract spindlesAnaphase B is different. Instead of chromosomes moving along the spindle, the spindle itself elongates, pushing the two poles farther apart and carrying the chromosomes with them. This elongation relies on molecular motors and on forces exerted from the cell cortex. Motor proteins in the overlap zone between spindle fibers slide those fibers apart. Simultaneously, dynein motors anchored at the cell’s outer membrane pull on fibers radiating from the poles. Measurements in human cells estimated the pulling force per individual fiber at roughly 6 piconewtons, consistent with each fiber being tugged by a single dynein motor.
8Developmental Cell. Direct force measurements reveal the mechanics of spindle orientation in human cellsInterestingly, not all the motors in the spindle midzone are pushers. The conserved kinesin-5 motor, which was long assumed to drive spindle elongation, actually acts as a brake during anaphase B in nematode embryos. Reducing its function made the spindle elongate faster, not slower, revealing that other motors or sliding mechanisms provide the primary driving force while kinesin-5 restrains the process.
9PubMed Central. Kinesin-5 acts as a brake in anaphase spindle elongationWhen the Usual Order Gets Reversed
Textbooks typically present anaphase A as happening first, with anaphase B following or overlapping. But biology does not always cooperate with textbook diagrams. In mouse egg cells, anaphase B actually precedes anaphase A. The loss of tension between sister chromosomes at anaphase onset creates a force imbalance that causes the spindle to elongate first, with chromosome-to-pole movement following afterward.
10Current Biology. Anaphase B Precedes Anaphase A in the Mouse EggMaize meiosis offers an even more striking departure. During both meiotic divisions in maize, chromosomes move toward the poles (anaphase A), but the spindle does not elongate at all. In fact, the spindle actually gets shorter after anaphase begins. Chromosome segregation in maize meiosis is accomplished entirely through anaphase A, with no visible contribution from anaphase B.
11Journal of Cell Science. Anaphase asymmetry and dynamic repositioning of the division plane during maize meiosisThese variations make it clear that the relative importance of the two sub-phases is not fixed by some universal blueprint but is tuned to the needs of each cell type and organism.
What Happens When Chromosomes Lag Behind
Not every chromosome makes it cleanly to its designated pole. The most common type of anaphase error involves a chromosome that gets stuck in the middle of the spindle while the rest move normally. These lagging chromosomes typically arise from an attachment defect called merotely, in which a single chromosome’s attachment site gets connected to fibers from both poles instead of just one. The spindle assembly checkpoint, effective as it is, cannot detect merotelic attachments because the chromosome is attached and under tension, just attached incorrectly.
12PubMed Central. Examining the role of lagging chromosomes in mitotic error and chromosomal instability in human cellsThe consequences of lagging chromosomes can range from harmless to catastrophic. A lagging chromosome that fails to rejoin the main group of chromosomes can end up enclosed in its own tiny nucleus, called a micronucleus, which is prone to DNA damage and can trigger cascading genomic rearrangements. However, most lagging chromosomes are actually corrected during anaphase and successfully rejoin the proper nucleus. In chromosomally stable human cells, about 9% displayed a transient lagging chromosome during anaphase, but only about 6% of those lagging chromosomes ended up forming a micronucleus. Even in chromosomally unstable cancer cells, where lagging chromosomes were far more frequent (about 44% of cells), only around 9% of the lagging chromosomes became micronuclei.
13Cell Reports. A Midzone-Based Aurora B Gradient Prevents Micronuclei Formation by Integrated Control of Anaphase Error Correction and Nuclear Envelope ReassemblyCells have a last-ditch correction mechanism active during anaphase itself. An enzyme called Aurora B, concentrated in the spindle midzone, creates a gradient of activity that helps detach the wrongly connected fibers from lagging chromosomes, giving them a chance to rejoin the correct side. This midzone-based error correction is a safety net that operates after the checkpoint has already been satisfied.
Anaphase Errors in Cancer
The link between anaphase errors and cancer is well established. Most solid tumors are aneuploid, meaning they carry abnormal chromosome numbers. Many of these tumors show ongoing chromosomal instability, a condition in which cells continue to mis-segregate whole chromosomes from one division to the next. This instability correlates with worse patient outcomes, likely because it generates the genetic diversity that lets tumor cell populations evolve resistance to treatment.
14PubMed Central. Mechanisms of chromosomal instabilityA significant proportion of the defects driving chromosomal instability in cancer converge on the same anaphase phenotype: lagging chromosomes in the spindle midzone. Beyond simple chromosome gains and losses, mis-segregation during anaphase can also produce chromatin bridges, in which stretched DNA connects the two separating groups of chromosomes. In cancer cells, these bridges and the resulting breakage can trigger cycles of chromosome breakage, fusion, and re-breakage that progressively scramble the genome.
15Cell. The Multifaceted Role of Chromosomal Instability in Cancer Some of these bridges persist into the final stages of division, and the resulting chromosome fragments can form micronuclei or get excluded from the newly forming nuclei entirely.16PubMed. Chromosomal instability and cytoskeletal defects in oral cancer cells
Chromosome mis-segregation during anaphase can also lead to highly complex, localized rearrangements called chromothripsis, in which a single chromosome trapped in a micronucleus gets shattered and reassembled in a scrambled order. These catastrophic events can activate cancer-driving genes in a single cell division, making anaphase errors not just a gradual source of instability but a potential trigger for rapid, dramatic genomic change.
Meiotic Anaphase and the Maternal Age Effect
The version of anaphase that occurs during meiosis, the specialized cell division that produces eggs and sperm, has additional complexity and additional vulnerability. In meiosis, cohesin must be removed in two stages. During the first division, cohesin along chromosome arms is cleaved while cohesin at the centromere is deliberately protected, keeping sister chromatids together. Only during the second division is centromeric cohesin removed. The protection depends on a phosphatase that counteracts the phosphorylation signals that separase needs to recognize its target. Recent work identified specific phosphorylation sites on the meiotic cohesin subunit Rec8 that control whether separase can cut it: one site promotes cleavage, while others promote protection, with a phosphatase actively removing the cleavage-promoting mark at the centromere.
17Cell Reports. Protection and deprotection of the Rec8 cohesin complex during meiosisThis system is particularly fragile in human eggs, and increasingly so with age. Human oocytes begin meiosis before birth and then arrest for decades. Beyond about age 35, the risk of aneuploidy rises sharply. A major reason is that cohesin, which must hold chromosomes together for the entire duration of that arrest, gradually deteriorates. Without adequate cohesin, chromosomes can separate prematurely or attach incorrectly, leading to errors at anaphase.
18PubMed Central. Meiosis and maternal aging: insights from aneuploid oocytes and trisomy birthsCohesin loss is not the only problem. Multiple mechanisms contribute to age-related meiotic errors, including failures in the recombination events that help hold chromosomes together, weakened checkpoint function, and changes in the spindle machinery itself.
19PubMed. Mechanisms of oocyte aneuploidy associated with advanced maternal age Errors can also arise during earlier stages of oocyte development, during the decades-long arrest period, or during the final resumption of meiosis, meaning there is no single point of failure but rather an accumulation of vulnerabilities across the entire lifespan of the egg cell.20PubMed Central. Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew
The clinical consequences are significant: increased infertility, higher rates of miscarriage, and elevated risk of conditions like trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and monosomy X (Turner syndrome). These outcomes trace directly back to what goes wrong at anaphase in aging eggs.
How Anaphase Sets Up the Final Cut
Anaphase does not just separate chromosomes. It also lays the groundwork for the physical splitting of the cell in two, a process called cytokinesis. As chromosomes move apart, the fibers remaining between them reorganize into a structure called the central spindle. This reorganization is driven by a protein complex called centralspindlin, a molecular machine that bundles antiparallel fibers together in the space between the separating chromosome masses.
21PubMed Central. Centralspindlin: at the heart of cytokinesisCentralspindlin is a four-protein assembly composed of a kinesin motor protein and a regulatory protein with a domain that controls Rho family signaling molecules. These signaling molecules, in turn, tell the cell cortex where to pinch inward to divide. The central spindle effectively acts as a spatial cue: by forming in the middle of the cell, right between the two chromosome groups, it positions the cleavage furrow so that each daughter cell receives one complete set of chromosomes.
22Developmental Cell. Centralspindlin: A Centrosome Component that Functions in CytokinesisThe coupling between anaphase and cytokinesis means that failures in central spindle assembly can lead to division failure even when chromosomes have separated correctly. Cells that cannot build a proper central spindle may end up with two nuclei in one cell body, a state that can promote chromosomal instability in subsequent divisions.
The Biochemistry of the Point of No Return
Once the APC/C destroys securin and cyclin B, the cell enters a distinct biochemical state. The major kinase that maintains the mitotic state, CDK1, loses its activity as cyclin B is degraded. But other kinases, particularly Aurora and Polo family kinases, persist during anaphase because their destruction depends on a different form of the APC/C that becomes active more slowly. This creates a unique window: the cell has exited the metaphase state but has not yet returned to a resting state. This transitional period is anaphase itself, and the persistence of Aurora and Polo kinases during this window is what allows the orderly sequence of events, from chromosome separation through central spindle assembly to the final cell cleavage, to proceed in the correct order.
23FEBS Letters. Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2ACounteracting these kinases are phosphatases, enzymes that remove the phosphate tags the kinases had added. The sequential reactivation of these phosphatases during anaphase and beyond is what ultimately restores the cell to its non-dividing state. The timing matters enormously. If phosphatases act too early, the cell may begin disassembling mitotic structures before chromosomes are safely partitioned. If they act too late, cells can stall in an extended anaphase or fail to complete cytokinesis.
Dividing More Than Just DNA
Chromosomes are not the only cellular contents that must be divided at anaphase. Organelles like mitochondria, the cell’s energy-producing compartments, also need to be distributed to both daughter cells. This is not left entirely to chance. A motor protein called Myo19, which sits on the outer surface of mitochondria, works with the cell’s actin network to ensure that mitochondria are partitioned roughly equally during anaphase. Without Myo19, mitochondrial segregation becomes uneven, and daughter cells can inherit very different numbers of these energy factories.
24Current Biology. Myo19 Ensures Symmetric Partitioning of Mitochondria and Coupling of Mitochondrial Segregation to Cell DivisionThis adds another dimension to anaphase. It is not solely a chromosome-sorting event but a whole-cell reorganization, in which the machinery for distributing DNA operates alongside independent systems for distributing organelles, signaling molecules, and structural components. The fact that these systems operate in parallel, each with its own molecular players, helps explain why anaphase, despite lasting only minutes, manages to produce two cells that are functional and viable rather than just two bags of randomly divided contents.