Cell Cycle and Mitosis

The Cell Cycle — An Overview

Part 1 of 7

Every living organism depends on cell division for growth, repair, and reproduction. The cell cycle is the ordered sequence of events that a cell undergoes from one division to the next.

A typical mammalian cell cycle lasts about 24 hours, though this varies enormously — some embryonic cells divide in 8 minutes, while liver cells may go years between divisions.

Phases of the Cell Cycle

The cell cycle consists of two major periods:

1. Interphase (~90% of the cell cycle)

• G(_1) phase (Gap 1) — cell growth, organelle duplication, preparation for DNA synthesis
• S phase (Synthesis) — DNA replication; each chromosome is duplicated into two sister chromatids joined at the centromere
• G(_2) phase (Gap 2) — continued growth, preparation for mitosis; error-checking of replicated DNA

2. Mitotic (M) phase (~10% of the cell cycle)

• Mitosis — division of the nucleus (karyokinesis) into two genetically identical daughter nuclei
• Cytokinesis — division of the cytoplasm to form two separate daughter cells

G(_0) Phase: Some cells exit the cell cycle and enter a quiescent state called G(_0). These cells are metabolically active but do not divide. Examples include neurons and mature muscle cells. Some G(_0) cells can re-enter the cycle if stimulated (e.g., hepatocytes after liver damage).

Checkpoint — Cell Cycle Overview

Chromosome Organization at Each Stage

Understanding chromosome structure throughout the cell cycle is critical:

Before S phase (G(_1)):

• Each chromosome = 1 DNA double helix + histones = unreplicated chromosome
• Human cell: 46 unreplicated chromosomes

After S phase (G(_2) and early mitosis):

• Each chromosome = 2 identical copies (sister chromatids) joined at the centromere = replicated chromosome
• Human cell: 46 replicated chromosomes (= 92 chromatids)
• The chromosome number does NOT change after replication — the cell still has 46 chromosomes

After mitosis:

• Sister chromatids separate → each becomes an independent chromosome
• Each daughter cell: 46 unreplicated chromosomes (identical to the original)

Key Distinction: "Chromosome number" counts centromeres, not chromatids. A replicated chromosome with two sister chromatids counts as ONE chromosome.

DNA packaging hierarchy:

1. DNA double helix (2 nm diameter)
2. DNA wraps around histone octamers → nucleosomes ("beads on a string," 11 nm)
3. Nucleosomes coil into 30 nm fiber (solenoid)
4. Looped domains of 30 nm fiber attached to a protein scaffold
5. Maximum condensation during metaphase → visible chromosomes (~1400 nm)

Checkpoint — Chromosome Counting

Key Terms — Cell Cycle

Match the Phase

Exit Ticket — Cell Cycle Phases

Interphase — Preparation for Division

Part 2 of 7

Interphase is often called the "resting phase," but this is a misnomer — the cell is extremely active during interphase. It is growing, producing proteins, duplicating organelles, and (during S phase) replicating its entire genome.

G(_1) Phase — Growth and Preparation

G(_1) is typically the longest and most variable phase of interphase:

Key events:

• Cell growth — increase in cell size and mass
• Synthesis of proteins, lipids, and carbohydrates
• Duplication of organelles (ribosomes, mitochondria, ER)
• Centriole duplication begins (in animal cells)
• Gene expression patterns establish the functional identity of the cell

G(_1)/S Checkpoint (Restriction Point):

• The most important checkpoint in the cell cycle
• The cell "decides" whether to commit to division
• Checks: adequate cell size, sufficient nutrients, growth factor signals, and intact DNA
• If the cell passes this checkpoint, it is committed to S phase and division
• If conditions are unfavorable, the cell enters G(_0)

Growth Factors: External signals (like PDGF, EGF, and insulin-like growth factor) bind to receptors and activate signaling cascades that promote passage through the G(_1)/S checkpoint. Cancer cells often have mutations that make them independent of growth factor signaling.

S Phase — DNA Replication

During S phase, the entire genome is copied:

Key events:

• Each chromosome is replicated by DNA polymerase using semi-conservative replication
• Replication begins at many origins of replication simultaneously (humans have ~30,000-50,000 origins)
• New histone proteins are synthesized and assembled onto the replicated DNA

Mitosis — Dividing the Nucleus

Part 3 of 7

Mitosis is the division of the nucleus to produce two genetically identical daughter nuclei. It is a continuous process but is conventionally divided into four (or five) stages: prophase, prometaphase, metaphase, anaphase, and telophase.

Prophase

Key events:

• Chromatin condenses into visible chromosomes (each consisting of two sister chromatids joined at the centromere)
• Condensation is driven by condensin proteins that coil and compact the chromatin
• The mitotic spindle begins to form:
  • In animal cells: centrosomes (each with two centrioles) migrate toward opposite poles; asters (radial arrays of microtubules) form around them
  • In plant cells: spindle forms without centrioles (acentrosomal spindle)
• Nucleolus disappears (ribosomal RNA synthesis ceases)

Prometaphase

Key events:

• Nuclear envelope breaks down (fragments into vesicles)
• Spindle microtubules now access the chromosomes
• Kinetochores form at the centromere of each sister chromatid — these are protein complexes that serve as attachment points for spindle microtubules
• Kinetochore microtubules from opposite poles attach to the kinetochores of sister chromatids
• Chromosomes are moved by motor proteins along microtubules in a "search and capture" process

Metaphase

Key events:

• All chromosomes align at the metaphase plate (the equator of the cell, equidistant from both poles)
• Each chromosome is attached to kinetochore microtubules from BOTH poles (bipolar attachment)

Cytokinesis — Dividing the Cytoplasm

Part 4 of 7

Cytokinesis is the division of the cytoplasm to produce two separate daughter cells. It typically begins during anaphase or telophase and overlaps with the final stages of mitosis.

The mechanism differs between animal and plant cells.

Cytokinesis in Animal Cells — Cleavage Furrow

Animal cells divide by cleavage:

1. A contractile ring of actin microfilaments and myosin II motor proteins assembles just beneath the plasma membrane at the former metaphase plate
2. The position of the contractile ring is determined by signals from the mitotic spindle (specifically, the central spindle — overlapping polar microtubules between the separating chromosomes)
3. Myosin II hydrolyzes ATP and slides along actin filaments, constricting the ring
4. This creates an inward indentation called the cleavage furrow
5. The furrow deepens progressively until the cell is pinched in two
6. Final separation (abscission) involves membrane fusion at the narrow bridge connecting the two cells

Why the middle? The position of the contractile ring is specified by signals from the spindle midzone and astral microtubules. The RhoA GTPase pathway activates myosin II and actin assembly at the equator. This ensures the cell divides between the two sets of chromosomes.

Cytokinesis in Plant Cells — Cell Plate

Plant cells cannot form a cleavage furrow because of their rigid cell wall. Instead, they build a new cell wall from the inside out:

1. Golgi-derived vesicles carrying cell wall materials (polysaccharides, glycoproteins) are transported along remaining spindle microtubules to the center of the cell
2. Vesicles fuse to form the cell plate, which grows outward from the center toward the existing cell wall
3. The cell plate matures into a new (shared layer between adjacent cell walls) and regions of new cell wall (primary wall)

Cell Cycle Regulation — Checkpoints and Cancer

Part 5 of 7

The cell cycle is tightly regulated to ensure accurate DNA replication and equal chromosome distribution. The control system relies on cyclins, cyclin-dependent kinases (Cdks), checkpoints, and tumor suppressors.

Loss of cell cycle control is the fundamental basis of cancer.

Cyclins and Cdks — The Engine of the Cell Cycle

Cyclin-dependent kinases (Cdks) are enzymes that phosphorylate target proteins to drive the cell through each phase. Cdks are only active when bound to a cyclin partner.

Key Cdk-cyclin complexes:

Problem-Solving Workshop — Cell Cycle

Part 6 of 7

This workshop applies cell cycle and mitosis concepts to experimental scenarios commonly seen on the AP Biology exam.

Scenario 1: Mitotic Index Calculation

A student observes 200 onion root tip cells under a microscope and counts the number of cells in each stage:

Mitotic Index = (cells in mitosis / total cells) (\times) 100

$\text{Mitotic Index} = \frac{14 + 6 + 4 + 6}{200} \times 100 = \frac{30}{200} \times 100 = 15\%$

AP Review — Cell Cycle and Mitosis

Part 7 of 7

Comprehensive AP-exam-style questions integrating all cell cycle and mitosis concepts.

Key Principles Summary

1. The cell cycle consists of interphase (G(_1), S, G(_2)) and M phase (mitosis + cytokinesis)
2. Mitosis produces two genetically identical daughter cells (preserving chromosome number)
3. Cyclin-Cdk complexes drive progression through each phase; cyclin degradation resets the system
4. Checkpoints (G(_1)/S, G(_2)/M, SAC) ensure accuracy before committing to the next phase
5. Cancer results from mutations in proto-oncogenes (gain of function) and tumor suppressors (loss of function)
6. Cytokinesis uses a cleavage furrow (animal) or cell plate (plant)

AP-Style Questions — Set 1

AP-Style Questions — Set 2

Comprehensive Matching

Final Review

Final Exit Ticket