Before Mitosis
Interphase — the cell prepares
Mitosis is brief. A typical mammalian cell spends most of its life in interphase — growing, functioning, and preparing molecular machinery for division. Interphase has three subphases:
G1 (Gap 1): cell grows, performs specialized functions, and monitors conditions. The G1 checkpoint (restriction point) assesses whether the cell is large enough, DNA is undamaged, and growth factors are present. If conditions are right, the cell commits to division. Cells that have stopped dividing permanently enter G0 — neurons and cardiac muscle cells spend most of their life there, which is why brain and heart injuries are so devastating.
S phase (Synthesis): DNA replication occurs. Each chromosome is copied — the two identical copies remain joined at the centromere as sister chromatids. After S phase the cell has 4N DNA content but still 46 chromosomes (each now consisting of 2 joined chromatids).
G2 (Gap 2): cell grows more and prepares mitotic machinery. The G2 checkpoint verifies DNA replication was accurate before allowing mitosis to begin.
G1 CK
The G1 restriction point — Rb and E2F
Rb (retinoblastoma protein) is the master brake of the cell cycle. In its active (unphosphorylated) state, Rb binds and inhibits the transcription factor E2F — blocking genes needed for S phase. When growth factors signal division: cyclin D accumulates → binds CDK4/6 → phosphorylates Rb → Rb releases E2F → E2F activates S phase genes → cell commits to division. Rb is mutated or inactivated in the majority of human cancers.
Memory trick: Rb = the cell cycle brakes. Phosphorylated Rb = brakes OFF = cell divides. Cancer removes the brakes.
The Four Phases
PMAT — what happens at each stage
The acronym PMAT (People Meet And Talk) helps remember the four phases in order.
💡 Cytokinesis — Splitting the Cytoplasm
Cytokinesis begins during late anaphase and completes after telophase:
Animal cells — cleavage furrow: An actin-myosin contractile ring assembles at the cell equator and constricts like a purse string, pinching the cell in two.
Plant cells — cell plate: A rigid cell wall prevents a furrow. Golgi vesicles containing cell wall material migrate to the center along the phragmoplast and fuse → cell plate grows from center outward → fuses with existing cell wall.
Result: Two genetically IDENTICAL diploid daughter cells — each with the same chromosome number as the parent (46 in human somatic cells). Compare meiosis: produces 4 genetically DIVERSE haploid cells (23 chromosomes) for reproduction.
P
Prophase — chromosomes condense, spindle assembles
Chromatin condenses into visible chromosomes — each consisting of two sister chromatids joined at the centromere. The nucleolus disappears. Two centrosomes migrate to opposite poles, extending microtubules to form the mitotic spindle. In late prophase (prometaphase), the nuclear envelope breaks down as nuclear lamins are phosphorylated and collapse. Kinetochore microtubules from both poles attach to kinetochore protein complexes on each centromere — biorientation must be achieved (microtubules from opposite poles attached to opposite kinetochores of each chromosome).
Memory trick: Prophase = Prepare. Chromosomes appear, spindle forms, nuclear envelope breaks down.
M
Metaphase — chromosomes align at the equator
Under tension from kinetochore microtubules pulling from both poles, chromosomes migrate to the metaphase plate — the imaginary plane equidistant between the two poles. The spindle assembly checkpoint (SAC) monitors kinetochore attachment: if even one kinetochore is unattached, MAD2 inhibits the APC/C ubiquitin ligase → anaphase is blocked. Once all chromosomes are bioriented under tension → SAC satisfied → APC/C released → anaphase proceeds.
Memory trick: Metaphase = Middle. All chromosomes line up in the MIDDLE. Spindle assembly checkpoint operates here.
A
Anaphase — sister chromatids pulled apart
APC/C activates separase, which cleaves cohesin proteins holding sister chromatids together. Kinetochore microtubules shorten by depolymerizing at the kinetochore end → each chromatid is pulled toward its pole. The chromatids are now individual chromosomes again. Non-kinetochore microtubules elongate and push poles apart, lengthening the cell. At anaphase end, each pole has a complete, identical set of chromosomes.
Memory trick: Anaphase = Apart. Sister chromatids are pulled APART to opposite poles.
T
Telophase — two new nuclei reform
Nuclear envelopes reassemble around each chromosome set at both poles using ER membrane fragments. Chromosomes decondense back into chromatin. Nucleoli reform. The spindle disassembles. The cell now contains two complete, identical nuclei — one at each end.
Memory trick: Telophase = Two nuclei. Nuclear division is complete. Everything that happened in prophase now happens in reverse.
🔬 Clinical Scenario — Cancer and Anti-Mitotic Drugs
Cancer is fundamentally unregulated mitosis. Anti-mitotic drugs are among the most important cancer therapies:
A
Normal cell: receives growth signal → G1 checkpoint passed → DNA replicated → G2 checkpoint passed → PMAT → cytokinesis → 2 daughter cells → growth signal withdraws → cells halt division.
B
Cancer cell: checkpoint proteins mutated (p53 lost, Rb inactivated, Ras constitutively active) → cell ignores signals to stop → continuous cycling → tumor growth. Loss of contact inhibition allows three-dimensional tumor expansion.
C
Vincristine and colchicine — both bind tubulin and prevent microtubule polymerization → no mitotic spindle can form → spindle assembly checkpoint is never satisfied → cell arrested at metaphase → apoptosis. Colchicine is used to arrest cells in metaphase for karyotyping. Vincristine treats leukemia and lymphoma.
D
Paclitaxel (Taxol) — opposite mechanism: stabilizes polymerized microtubules and prevents depolymerization → spindle cannot shorten in anaphase → chromosomes cannot be pulled to poles → cell arrested → apoptosis. Used for breast, ovarian, and lung cancers. Both vincristine and Taxol exploit the fact that rapidly dividing cancer cells spend more time in mitosis than normal cells.
📌 Exam Application
Mitosis is tested extensively. Know these precisely:
1. PMAT in order — Prophase (condense, spindle, nuclear envelope breakdown), Metaphase (align at plate), Anaphase (chromatids pulled apart), Telophase (nuclear envelope reforms, decondense).
2. Spindle assembly checkpoint — monitors biorientation at METAPHASE. If any kinetochore unattached → cell held at metaphase. Vincristine and Taxol both arrest cells here (from opposite mechanisms).
3. Cytokinesis — animal: cleavage furrow (actin-myosin ring). Plant: cell plate (Golgi vesicles).
4. Result — 2 identical diploid daughter cells. NOT the same as meiosis (4 haploid cells for reproduction).
5. Cancer connection — checkpoints lost → uncontrolled division. G1 checkpoint: Rb/E2F. G2: ATM/Chk. M: SAC/APC-C.
⚠️ The Most Common Mitosis Mistakes
Chromosome count during mitosis: The cell has 46 chromosomes before, during, and after mitosis. In S phase, chromosomes are duplicated into sister chromatids — but this DOES NOT change the chromosome count. Each chromosome still consists of two chromatids joined at the centromere. In anaphase you temporarily have 92 chromatids (each called a chromosome), but each daughter cell receives 46 — same as the parent.
Mitosis vs meiosis: Mitosis separates SISTER CHROMATIDS (identical copies). Meiosis I separates HOMOLOGOUS CHROMOSOMES (maternal from paternal). Mitosis = 2 diploid daughter cells for growth and repair. Meiosis = 4 haploid cells for reproduction.
Vincristine vs Taxol mechanisms: Vincristine prevents polymerization (no spindle forms). Taxol prevents depolymerization (spindle cannot function). Both arrest cells in metaphase via the spindle assembly checkpoint. Students often confuse which drug does what.
✓ Quick Self-Test
1. What are the four phases of mitosis in order and what happens in each?
2. What does the spindle assembly checkpoint monitor and what happens if it is not satisfied?
3. How does cytokinesis differ between animal and plant cells?
4. What is the result of one complete mitotic division?
5. How do vincristine and paclitaxel (Taxol) both arrest cells in mitosis despite having opposite mechanisms?
Answers:
1. Prophase: chromosomes condense, spindle forms, nuclear envelope breaks down. Metaphase: chromosomes align at the metaphase plate. Anaphase: sister chromatids pulled to opposite poles. Telophase: nuclear envelopes reform, chromosomes decondense.
2. The SAC monitors whether all kinetochores are bioriented — properly attached to spindle microtubules from both poles and under tension. If any kinetochore is unattached, MAD2 inhibits APC/C → anaphase is blocked. Failure leads to chromosomal missegregation → aneuploidy → cancer.
3. Animal cells: actin-myosin contractile ring forms a cleavage furrow that pinches the cell in two. Plant cells: Golgi vesicles fuse at the cell center to form a cell plate that grows outward and becomes the new cell wall.
4. Two genetically identical diploid daughter cells with the same chromosome number as the parent cell.
5. Vincristine prevents tubulin polymerization → no spindle can form → SAC is never satisfied → cell arrested. Taxol prevents microtubule depolymerization → spindle cannot shorten → chromosomes cannot be pulled to poles → SAC cannot be satisfied → cell arrested. Both ultimately trigger apoptosis.