Mitosis unfolds in six recognizable phases: prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis. Together they take a single cell’s duplicated set of chromosomes, split them into two identical groups, and package each group inside its own new cell. The whole process can finish in under an hour in rapidly dividing human cells, yet the molecular choreography at each stage is precise enough that errors occur in fewer than one in every ten thousand divisions in healthy tissue. Understanding what happens at each phase, and what the cell does to police itself along the way, goes a long way toward making sense of everything from wound healing to cancer.
Getting Ready Before Mitosis Begins
Before a cell enters mitosis it has already copied every chromosome during a preparatory period called S phase. By the time it reaches the boundary between the G2 phase and mitosis proper, it holds two complete copies of its genome, each pair of duplicates physically glued together as sister chromatids. The cell does not simply flip a switch to start dividing. It relies on the activation of a master enzyme called Cdk1, which partners with a protein called Cyclin B. This partnership is the universal trigger: once the Cdk1-Cyclin B complex is active, it phosphorylates dozens of target proteins throughout the cell, setting off the cascade of structural changes that define the first visible phase of mitosis.1PubMed Central. The G2-to-M transition from a phosphatase perspective: a new vision of the meiotic division
Prophase
Prophase is the opening act, and its most dramatic feature is visible even under a basic light microscope: the long, tangled threads of DNA condense into thick, compact chromosomes. This condensation is not just a matter of tidiness. Compacting the DNA protects it from breakage during the physical pulling that comes later. The process depends on chemical modifications to histone proteins, the spools around which DNA is wound. Phosphorylation of one particular histone, histone H3, plays a direct role in driving this condensation.2PubMed. Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation
Meanwhile, two other things are happening at the edges of the cell. The centrosomes, which duplicated earlier alongside the chromosomes, begin migrating toward opposite sides of the cell. As they travel, they start assembling microtubules, the protein filaments that will eventually form the spindle apparatus. You can think of each centrosome as a pole of a globe, with the microtubules radiating outward like lines of longitude. At this stage, the nuclear envelope is still intact, so the chromosomes and the spindle exist in separate compartments.
Prometaphase
Prometaphase begins when the nuclear envelope breaks apart. This is not a gentle dissolution; it is an active demolition driven by the same Cdk1-Cyclin B complex that launched mitosis. That complex phosphorylates the lamin proteins that form the structural scaffold of the nuclear envelope, causing the lamina to depolymerize and the envelope to fragment into small membrane pieces.3PubMed Central. Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies Without its protective shell, the chromosomes are suddenly exposed to the cytoplasm and, crucially, to the growing microtubules of the spindle.
What follows is sometimes described as “search and capture.” Microtubules extend outward from the spindle poles, growing and shrinking rapidly, probing the cell until they connect with a specialized protein structure on each chromosome called the kinetochore. Each sister chromatid has its own kinetochore, and the goal is for microtubules from opposite poles to attach to opposite sisters. This connection is how the cell will eventually pull the sister chromatids apart. The process is progressive: chromosomes closer to a pole get captured first, and those farther away take longer, leading to the jostling, seemingly chaotic movement of chromosomes that defines this phase.4PubMed Central. Thirty years of search and capture: The complex simplicity of mitotic spindle assembly
Metaphase
Metaphase is the point of alignment. All the chromosomes line up along the middle of the cell, a position called the metaphase plate. This lineup is not decorative; it reflects the fact that each chromosome is now attached to microtubules from both spindle poles, with equal pulling forces from each side holding it in the center. The tension across each pair of sister kinetochores is the cell’s way of confirming that the attachment is correct. When tension is high, it signals that both kinetochores are properly connected to opposite poles. When tension is low or absent, the attachment is probably wrong, and the cell destabilizes it so the microtubule can release and try again.5PubMed Central. The importance of microtubule-dependent tension in accurate chromosome segregation
The enzyme that reads this tension signal is Aurora B kinase, which sits at the inner centromere between the two sister kinetochores. When a kinetochore is correctly attached and under tension, it physically stretches away from Aurora B, moving out of range of the enzyme’s activity. When the attachment is wrong and tension is low, the kinetochore stays close enough for Aurora B to phosphorylate key targets, which loosens the microtubule grip and forces a do-over.6PubMed Central. Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates Experiments that artificially reduced tension at kinetochores confirmed this relationship directly: lower tension led to higher rates of microtubule detachment and more chromosome mis-segregation, in a dose-dependent way.7Developmental Cell. Tension-Dependent Kinetochore Phosphorylation and the Spindle Checkpoint Define a Mechanism for Bi-orientation Sensing during Mitosis
The Spindle Assembly Checkpoint
Metaphase is also where the cell’s most important quality-control mechanism operates: the spindle assembly checkpoint. This checkpoint is not a separate phase, but it dominates the timing of metaphase. As long as even a single kinetochore remains unattached, it generates a biochemical “wait” signal that prevents the cell from moving into anaphase. The signal is only silenced when every kinetochore in the cell is properly connected to spindle microtubules.8PubMed Central. Spindle assembly checkpoint activation and silencing at kinetochores This makes metaphase potentially the longest phase of mitosis in absolute time: a cell with all chromosomes correctly bi-oriented passes through in minutes, but a cell with one stubborn misattachment can sit at this checkpoint for an hour or more.
The checkpoint works by blocking a molecular trigger called the anaphase-promoting complex. Once every chromosome is accounted for and properly attached, that block is lifted, and the cell commits irreversibly to splitting its chromosomes. There is no going back after this point.
Anaphase
Anaphase is the most visually striking phase and the briefest. It happens in two overlapping sub-steps. In the first, an enzyme called separase cleaves the cohesin proteins that have been holding sister chromatids together since they were first made. With the glue gone, the sisters are free to move apart, pulled toward opposite poles by the shortening of their attached microtubules.9PubMed Central. The protease activity of yeast separase (esp1) is required for anaphase spindle elongation independently of its role in cleavage of cohesin
In the second sub-step, the spindle itself elongates. The overlapping microtubules in the middle of the spindle slide apart, pushing the two poles farther from each other and dragging the newly separated chromosomes along. This elongation involves motor proteins sliding antiparallel microtubules outward, plus pulling forces at the cell cortex from proteins that tug on microtubules reaching toward the cell’s edges.10PubMed Central. Anaphase B The combined effect of both sub-steps is fast and decisive: chromosomes move at roughly one to two micrometers per minute, and the entire separation is usually complete within a few minutes.
Telophase
Once the chromosomes arrive at opposite poles, the cell begins to reverse many of the changes it made during prophase. The chromosomes start to de-condense, loosening back into the extended form that allows genes to be read and used. At the same time, a new nuclear envelope assembles around each cluster of chromosomes. Membrane fragments left over from the original envelope’s destruction, along with fresh membrane from the cell’s internal stores, wrap around the chromatin, and new nuclear pore complexes are assembled into the growing envelope to restore transport between the nucleus and cytoplasm.11PubMed Central. Building a nuclear envelope at the end of mitosis: coordinating membrane reorganization, nuclear pore complex assembly, and chromatin de-condensation
Telophase effectively produces two nuclei sitting inside what is still one cell. Each nucleus contains a full, identical set of chromosomes. The spindle microtubules disassemble, and the lamin proteins that were dismantled during prometaphase are dephosphorylated so they can re-polymerize and form new nuclear laminas, giving each nucleus its structural integrity back.
Cytokinesis
Cytokinesis is the physical splitting of one cell into two. In animal cells, this is driven by a ring of actin and myosin filaments, called the contractile ring, that assembles just beneath the plasma membrane at the cell’s equator during anaphase. The ring contracts like a drawstring, pulling the membrane inward to form a visible indentation called the cleavage furrow. As the furrow deepens, it pinches the cell in half, dividing the cytoplasm and all its contents roughly equally between the two daughter cells.12PubMed Central. The contractile ring
Cytokinesis usually overlaps with telophase rather than waiting until it finishes. By the time the nuclear envelopes are fully rebuilt, the cleavage furrow is often well on its way. The positioning of the contractile ring is determined by signals from the spindle itself: the midzone, where the antiparallel microtubules overlap in the center, tells the cell cortex where to assemble the ring. This ensures the division happens between the two chromosome sets, not through one of them.
How Plant Cells Handle It Differently
Plant cells cannot pinch themselves in half because they are surrounded by a rigid cell wall. Instead of a contractile ring, they build a brand-new wall between the two daughter cells from the inside out. The structure responsible is called the phragmoplast, which forms between the two daughter nuclei during the transition from anaphase to telophase. It consists of microtubules, actin filaments, and membrane compartments that guide the delivery of wall-building materials. Vesicles carrying cell-wall components fuse at the center, forming a structure called the cell plate, which grows outward until it reaches the existing cell wall at the edges.13PubMed Central. Phragmoplast microtubule dynamics – a game of zones
Another difference is that many plant cells lack centrosomes entirely. They still form spindles and segregate chromosomes accurately, but the microtubules are organized by other structures distributed across the cell. Some organisms go even further: certain yeasts undergo what is called “closed” mitosis, meaning the nuclear envelope never breaks down at all. The spindle forms inside the nucleus, and chromosome separation happens entirely within the intact envelope. Mammals, by contrast, perform “open” mitosis, with full envelope breakdown and reformation.14Current Biology. Deciphering the Evolutionary History of Open and Closed Mitosis These variations are a reminder that mitosis is not a single rigid recipe. The core logic of duplicating and dividing chromosomes is universal, but organisms have evolved distinct mechanical solutions to carry it out.
When Mitosis Goes Wrong
The spindle assembly checkpoint catches most errors, but it is not perfect. When a chromosome does slip through with the wrong attachment or fails to separate properly, the result is aneuploidy: one daughter cell ends up with too many chromosomes, and the other with too few. This is the single most common chromosomal abnormality in human cancers, and the connection between mitotic errors and tumor development was first proposed by Theodor Boveri more than a century ago.15PubMed Central. Boveri and beyond: Chromothripsis and genomic instability from mitotic errors
More recent work has revealed that the consequences of mitotic mistakes can be even more dramatic than simply gaining or losing a whole chromosome. A mis-segregated chromosome can end up enclosed in a small, defective structure called a micronucleus rather than being incorporated into a proper daughter nucleus. Inside this fragile compartment, the chromosome’s nuclear envelope is unstable and prone to rupture, which exposes the DNA to enzymes in the cytoplasm. The result can be chromothripsis, a catastrophic event in which the chromosome is shattered into fragments and reassembled incorrectly, generating dozens or even hundreds of mutations in a single cell cycle.15PubMed Central. Boveri and beyond: Chromothripsis and genomic instability from mitotic errors This kind of localized genomic chaos has been found across many cancer types and can accelerate tumor evolution far more rapidly than the slow accumulation of individual mutations.
Anti-Mitotic Cancer Drugs
Because cancer cells divide more frequently than most healthy cells, mitosis has been a target for cancer therapy for decades. The oldest and still most widely used class of anti-mitotic drugs targets tubulin, the protein that makes up microtubules. Drugs like taxanes stabilize microtubules so they cannot shorten properly, while vinca alkaloids prevent microtubules from assembling in the first place. Both approaches sabotage the spindle, activate the spindle assembly checkpoint, and trap cells in a prolonged mitotic arrest that often leads to cell death. These drugs are effective, but because tubulin also serves structural and transport roles in non-dividing cells, they come with significant side effects including nerve damage and low blood counts.16Nature Reviews Cancer. Targeted anti-mitotic therapies: can we improve on tubulin agents?
To get around this problem, researchers have been developing a newer generation of drugs that target proteins with roles specific to mitosis and no essential function in resting cells. These include inhibitors of mitotic kinases and motor proteins like kinesin, as well as compounds that interfere with checkpoint signaling or DNA damage responses during division.17PubMed Central. Small-Molecule Mitotic Inhibitors as Anticancer Agents: Discovery, Classification, Mechanisms of Action, and Clinical Trials The hope is that by targeting mitosis-specific machinery, the new drugs can kill dividing cancer cells while leaving non-dividing healthy cells alone. Some of these agents are in clinical trials; none have yet displaced the tubulin-targeting drugs in standard treatment, but the approach continues to attract serious investment.
Asymmetric Division and Stem Cells
Not every mitotic division produces two identical daughter cells. Stem cells in tissues like the gut lining, blood-forming bone marrow, and skin frequently perform asymmetric divisions, in which the mitotic machinery is deliberately oriented so that the two daughters inherit different fates. One daughter remains a stem cell, preserving the tissue’s regenerative capacity, while the other commits to specializing into a mature cell type. The mechanisms that achieve this are tightly linked to the mitotic spindle: the orientation of the spindle determines where the division plane falls, and proteins concentrated on one side of the cell are partitioned unequally as a result.18PubMed Central. Cellular and molecular mechanisms of asymmetric stem cell division in tissue homeostasis
This capacity for asymmetric division is what allows tissues to maintain themselves over a lifetime. If every stem cell division produced two identical daughters, the tissue would either expand uncontrollably or exhaust its stem cell supply. By toggling between symmetric expansion (two stem cells) and asymmetric maintenance (one stem cell, one specialized cell), the body balances growth with stability. When the mechanisms controlling spindle orientation go awry, the balance tips, and the result can be tissue degeneration on one end or tumor formation on the other. The mitotic spindle, far from being just a chromosome-separating machine, turns out to be a key instrument of cell-fate decisions throughout the body.