Phases of the Cell Cycle

Why This Matters

The cell cycle is the foundation of how organisms grow, repair damage, and reproduce—and it's one of the most heavily tested topics in Cell Biology. You're not just being asked to memorize a sequence of phases; you're being tested on why cells have checkpoints, how molecular signals control division timing, and what happens when this process goes wrong (hint: cancer). Understanding the cell cycle means understanding how a single fertilized egg becomes a complex organism and why some cells divide constantly while others never divide at all.

The key concepts here—cell cycle regulation, DNA replication fidelity, and chromosome segregation—connect directly to genetics, cancer biology, and development. When you study these phases, focus on the molecular machinery driving each transition and the checkpoints that prevent errors. Don't just memorize "prophase comes before metaphase"—know what must happen at each stage and what would go wrong if it didn't.

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Growth and Preparation: Interphase

Before a cell can divide, it must grow, duplicate its DNA, and prepare the molecular machinery for division. Interphase comprises approximately 90% of the cell cycle and involves three distinct subphases, each with specific tasks that must be completed before proceeding.

G1 Phase (First Gap)

• Primary growth phase—the cell increases in size, synthesizes proteins, and produces new organelles to support future division
• G1 checkpoint (Restriction Point) evaluates cell size, nutrient availability, and DNA integrity before committing to division
• Cyclin D levels rise during G1, partnering with CDK4/6 to push the cell toward S phase

S Phase (Synthesis)

• DNA replication occurs—each chromosome is duplicated to form two identical sister chromatids joined at the centromere
• Semi-conservative replication means each new DNA molecule contains one original strand and one newly synthesized strand
• Replication errors are monitored by DNA polymerase proofreading and mismatch repair systems, maintaining genetic fidelity

G2 Phase (Second Gap)

• Final preparation for mitosis—the cell continues growing and synthesizes proteins needed for chromosome segregation
• G2 checkpoint verifies that DNA replication is complete and scans for any remaining DNA damage
• Cyclin B accumulates and activates CDK1, forming the maturation-promoting factor (MPF) that triggers entry into mitosis

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Division of the Nucleus: Mitosis

Mitosis is the choreographed separation of duplicated chromosomes into two identical nuclei. The process relies on the mitotic spindle—a dynamic structure of microtubules that physically moves chromosomes to opposite poles of the cell.

Prophase

• Chromatin condenses into visible chromosomes—this compaction prevents tangling and breakage during segregation
• Nuclear envelope breakdown occurs as the envelope fragments, allowing spindle fibers access to chromosomes
• Centrosomes migrate to opposite poles and begin nucleating spindle microtubules

Metaphase

• Chromosomes align at the metaphase plate—the cell's equatorial plane, equidistant from both poles
• Kinetochore attachment connects each sister chromatid to spindle fibers from opposite poles (bipolar attachment)
• Spindle assembly checkpoint (M checkpoint) halts progression until all chromosomes are properly attached, preventing aneuploidy

Anaphase

• Sister chromatids separate—the enzyme separase cleaves cohesin proteins holding them together
• Motor proteins walk along microtubules, pulling chromatids toward opposite poles at roughly 1 μm per minute
• Anaphase A vs. Anaphase B—chromatids move poleward (A) while poles themselves move apart (B), both contributing to separation

Telophase

• Nuclear envelopes reform around each set of chromosomes using fragments from the original envelope
• Chromosomes decondense back into diffuse chromatin, allowing gene expression to resume
• Cytokinesis typically begins during late telophase, overlapping with nuclear reformation

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Division of the Cytoplasm: Cytokinesis

Cytokinesis physically separates the cytoplasm to produce two daughter cells. The mechanism differs dramatically between animal and plant cells due to the presence of a rigid cell wall in plants.

Cytokinesis in Animal Cells

• Contractile ring forms—a band of actin and myosin filaments assembles just beneath the plasma membrane at the former metaphase plate
• Cleavage furrow deepens as the ring contracts, pinching the cell inward like a drawstring bag
• Abscission completes division—membrane fusion separates the two daughter cells entirely

Cytokinesis in Plant Cells

• Cell plate forms from the inside out—vesicles from the Golgi apparatus fuse at the cell's center
• Vesicles deliver cell wall materials including pectin and hemicellulose to build the new partition
• Cell plate expands outward until it fuses with the existing plasma membrane and cell wall

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Cell Cycle Regulation: Checkpoints and Molecular Control

The cell cycle isn't automatic—it's controlled by molecular signals that act as quality control inspectors. Cyclins and CDKs form the core regulatory machinery, while checkpoints serve as decision points that can halt the cycle if problems are detected.

Cell Cycle Checkpoints

• G1 checkpoint (Restriction Point)—the primary decision point determining whether the cell commits to division or exits to G0
• G2 checkpoint prevents entry into mitosis if DNA is damaged or incompletely replicated
• M checkpoint (Spindle Assembly Checkpoint) ensures all chromosomes have proper bipolar attachment before anaphase begins

Cyclins and Cyclin-Dependent Kinases (CDKs)

• CDKs are always present but remain inactive without their cyclin partners—cyclins are the regulatory subunit
• Cyclin levels oscillate throughout the cycle, rising and falling to activate CDKs at specific times
• CDK phosphorylation of target proteins triggers transitions between phases—for example, MPF (Cyclin B-CDK1) initiates mitosis

G0 Phase (Quiescent State)

• Exit from the active cell cycle—cells in G0 are not preparing to divide but remain metabolically active
• Reversible or permanent depending on cell type—muscle and nerve cells are permanently in G0, while liver cells can re-enter the cycle
• Triggered by lack of growth factors or other signals indicating division is unnecessary or inappropriate

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Molecular Events: DNA and Chromosome Dynamics

Several molecular processes must occur with precision for successful cell division. These events ensure genetic information is accurately copied and physically organized for segregation.

DNA Replication (S Phase)

• Origins of replication are specific DNA sequences where replication begins—human cells have thousands to speed the process
• DNA polymerase synthesizes new strands in the $5' \rightarrow 3'$ direction, using each original strand as a template
• Leading and lagging strands are synthesized differently—continuous vs. Okazaki fragments—due to antiparallel DNA structure

Chromosome Condensation

• Condensin complexes drive chromosome compaction by creating loops in the chromatin fiber
• 10,000-fold compaction transforms diffuse chromatin into compact chromosomes visible under a light microscope
• Essential for segregation—without condensation, chromosomes would tangle and break during anaphase

Spindle Formation and Function

• Centrosomes serve as microtubule organizing centers (MTOCs)—each contains a pair of centrioles surrounded by pericentriolar material
• Three types of spindle microtubules: kinetochore fibers (attach to chromosomes), polar fibers (overlap at center), and astral fibers (anchor to cell cortex)
• Dynamic instability allows microtubules to grow and shrink rapidly, facilitating chromosome capture and movement

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Quick Reference Table

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Self-Check Questions

1. Which two checkpoints both assess DNA damage, and how do their roles differ in terms of when during the cycle they act?

2. A cell treated with a drug that prevents cyclin B degradation would arrest at which phase, and why?

3. Compare and contrast cytokinesis in animal cells versus plant cells—what structural difference explains why they use different mechanisms?

4. If the spindle assembly checkpoint failed to function, what specific error would occur during mitosis, and what would be the consequence for daughter cells?

5. A liver cell in G0 receives growth factor signals after tissue injury. Trace the molecular pathway (including specific cyclins and CDKs) that would allow this cell to re-enter the cell cycle and eventually divide.