Mitosis Explained: How Cells Divide to Grow and Repair

Why Cells Divide

Cell division by mitosis serves several essential biological functions. During embryonic development, a single fertilized egg must divide repeatedly to produce the roughly 37 trillion cells in an adult human body. After development is complete, mitosis continues to replace cells that are damaged, worn out, or naturally shed. The cells lining the human intestine are replaced every three to five days, skin cells are replaced every two to three weeks, and red blood cells are replaced roughly every 120 days. An adult human body produces approximately 3.8 million new cells every second through mitosis to maintain these tissues.

Mitosis is also the basis of asexual reproduction in many organisms. Single-celled eukaryotes like amoebas and paramecia reproduce by mitotic division, creating daughter cells that are genetic clones of the parent. Many plants can propagate through mitotic processes, producing runners, tubers, or bulbs that grow into genetically identical offspring. Even some animals, including certain starfish and hydra, can reproduce asexually through mitosis-based processes like budding and fragmentation.

Preparing for Division: S Phase and G2

Before a cell can divide, it must duplicate its entire genome during S (synthesis) phase of the cell cycle. DNA replication produces two identical copies of each chromosome, which remain joined at a region called the centromere as sister chromatids. The cohesion between sister chromatids is maintained by a ring-shaped protein complex called cohesin, which holds the two copies together until they are separated during anaphase.

During G2 phase, the cell checks the integrity of the replicated DNA and prepares the molecular machinery needed for division. Centrosomes, the organelles that organize the mitotic spindle, are duplicated during S phase and begin to move toward opposite sides of the cell during G2. The cell also synthesizes proteins needed for spindle assembly, chromosome condensation, and the regulatory kinases that drive the transition into mitosis.

Prophase: Chromosomes Condense

Prophase is the first visible stage of mitosis, during which the diffuse chromatin fibers condense into compact, well-defined chromosomes. This condensation is driven by condensin protein complexes that compact the chromatin into loops, progressively coiling it into the characteristic X-shaped structures visible under a light microscope. Each chromosome at this stage consists of two sister chromatids joined at the centromere.

Meanwhile, the two centrosomes begin migrating toward opposite poles of the cell, pushed apart by the elongation of microtubules between them. Each centrosome nucleates a radial array of microtubules called an aster, and together the growing microtubule arrays begin to form the mitotic spindle. In the nucleus, the nucleolus disappears as ribosomal RNA transcription ceases and the nucleolar components disperse.

Prometaphase: The Nuclear Envelope Breaks Down

During prometaphase, the nuclear envelope disassembles as the lamins of the nuclear lamina are phosphorylated and depolymerize. The nuclear membrane fragments into vesicles, exposing the chromosomes to the cytoplasm and allowing spindle microtubules to access them. Each chromosome has a specialized protein structure called a kinetochore assembled at its centromere region. Kinetochores serve as attachment points for spindle microtubules, and each sister chromatid has its own kinetochore facing opposite directions.

Microtubules extending from opposite spindle poles capture kinetochores through a search-and-capture mechanism: microtubules grow outward from the centrosomes, shrink back, and grow again in random directions until they encounter and attach to a kinetochore. Once both sister chromatids are attached to microtubules from opposite poles (a state called bi-orientation), the chromosome begins to move toward the center of the cell. The process of achieving bi-orientation for all chromosomes typically takes 10 to 20 minutes in mammalian cells.

Metaphase: Chromosomes Align

In metaphase, all chromosomes are aligned at the metaphase plate, an imaginary plane equidistant between the two spindle poles. The alignment is not passive; it results from a tug-of-war between microtubules pulling each sister chromatid toward opposite poles. When the pulling forces are balanced, the chromosome oscillates gently at the cell equator.

The spindle assembly checkpoint (SAC), also known as the mitotic checkpoint, monitors the attachment of kinetochores to microtubules and prevents the cell from proceeding to anaphase until every chromosome is properly bi-oriented. Even a single unattached kinetochore generates a "wait" signal that inhibits the anaphase-promoting complex/cyclosome (APC/C), the enzyme complex that triggers the next stage. This checkpoint is critical for genomic stability: cells that bypass it frequently mis-segregate chromosomes, producing daughter cells with abnormal chromosome numbers, a condition called aneuploidy.

Anaphase: Sister Chromatids Separate

Once the spindle assembly checkpoint is satisfied, the APC/C triggers the destruction of securin, a protein that inhibits the enzyme separase. Freed separase then cleaves the cohesin rings holding sister chromatids together, allowing them to separate. Anaphase occurs in two overlapping phases. During anaphase A, the separated chromatids (now called daughter chromosomes) are pulled toward opposite poles by the shortening of kinetochore microtubules. During anaphase B, the spindle poles themselves move further apart as interpolar microtubules slide against each other and push the poles away from the cell center.

Anaphase is remarkably fast, typically lasting only 5 to 10 minutes. The chromosomes move at speeds of roughly 1 micrometer per minute, driven by a combination of microtubule depolymerization at the kinetochore (which shortens the attached microtubules) and motor proteins that walk along microtubules toward the spindle poles. The precision of this process is extraordinary: errors in chromosome segregation occur in fewer than 1 in 100,000 cell divisions in normal tissues.

Telophase and Cytokinesis: Two Cells Form

During telophase, the separated chromosomes arrive at the spindle poles and begin to decondense back into diffuse chromatin. New nuclear envelopes assemble around each set of chromosomes from the membrane vesicles and ER fragments present in the cytoplasm. The nuclear lamina reforms, nuclear pores are rebuilt, and the nucleolus reappears as rRNA transcription resumes. By the end of telophase, two distinct nuclei have formed within the single cell.

Cytokinesis, the physical division of the cytoplasm, typically overlaps with telophase. In animal cells, a contractile ring of actin and myosin filaments assembles beneath the plasma membrane at the cell equator. The ring contracts inward like a purse string, creating a cleavage furrow that deepens until the cell is pinched into two separate daughter cells. In plant cells, which have rigid cell walls, cytokinesis occurs by the construction of a cell plate: vesicles derived from the Golgi apparatus accumulate at the cell center and fuse to form a new cell wall and membrane that partitions the cell into two.

When Mitosis Goes Wrong

Errors in mitosis can have serious consequences. If the spindle assembly checkpoint fails and chromosomes are mis-segregated, the resulting aneuploidy can lead to cell death, developmental abnormalities, or cancer. Most human cancers exhibit some degree of chromosomal instability, characterized by an elevated rate of chromosome gain or loss during mitosis. Certain tumor suppressor genes, including TP53 and RB1, play direct roles in ensuring proper cell cycle progression and division; their inactivation is among the most common genetic events in cancer development.

Aneuploidy arising during meiosis (rather than mitosis) is the leading cause of spontaneous miscarriage in humans and is responsible for conditions like Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13). The risk of meiotic errors increases with maternal age, which is why the incidence of these conditions rises in pregnancies of older mothers.