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Cell Biology Unit 7: The Cell Cycle and Its Control

This unit explains how cells copy their DNA, divide it equally, and use cyclin–Cdk engines and checkpoints to make sure each step happens once, in order, and only when conditions are right.

Covers: Phases of the cell cycle, Cyclins, Cdks and their regulation, G1/S control: Rb, E2F and the restriction point, DNA damage checkpoints and p53, Mitosis and the spindle assembly checkpoint, APC/C, securin, separase and cohesin, Cytokinesis

Study guide

The eukaryotic cell cycle has four phases: G1 (growth and decision), S (DNA replication), G2 (preparation and checks) and M (mitosis plus cytokinesis). Cells that stop dividing enter a resting state called G0. In an asynchronous culture, the fraction of cells in a phase roughly reflects its relative length, and flow cytometry sorts cells by DNA content: G1 cells have 2C, G2 and M cells have 4C, and S-phase cells lie between. After S phase, each chromosome has two sister chromatids held together by cohesin, so a human G2 cell has 46 chromosomes but 92 chromatids.

The cell-cycle control system is built on cyclin-dependent kinases (Cdks), which are active only when bound to a cyclin. Different cyclins rise and fall: cyclin D with Cdk4/6 in G1, cyclin E with Cdk2 at G1/S, cyclin A in S, and cyclin B with Cdk1 for mitosis. Cdk activity is also set by phosphorylation: CAK adds an activating phosphate, Wee1 adds an inhibitory one, and Cdc25 removes it. Cdk inhibitors such as p16, p21 and p27 bind and block Cdks. Ubiquitin ligases end each phase by destroying proteins: SCF acts at G1/S and APC/C acts in mitosis.

Classic experiments built this picture. Fusing a G1 cell with an S-phase cell made the G1 nucleus replicate early, revealing diffusible activators. Injecting mitotic frog egg cytoplasm into G2 oocytes triggered mitosis, identifying MPF, later shown to be Cdk1–cyclin B. Yeast cdc mutants identified genes such as cdc2 (Cdk1) and wee1. In mammalian G1, mitogens raise cyclin D; cyclin D–Cdk4/6 starts phosphorylating Rb, releasing E2F, which turns on cyclin E and S-phase genes. Positive feedback past the restriction point commits the cell to divide even if mitogens disappear.

Checkpoints stop the cycle when something is wrong. DNA damage activates ATM and ATR kinases, which stabilize p53; p53 induces p21, blocking G1/S-Cdks, and can also trigger apoptosis. Damage in G2 blocks Cdc25, keeping Cdk1 inhibited. Mitosis proceeds through prophase (condensation), prometaphase (envelope breakdown and kinetochore capture), metaphase (alignment), anaphase (sister separation) and telophase (nuclear reformation). The spindle assembly checkpoint senses unattached kinetochores and uses Mad2 to block Cdc20–APC/C, so anaphase waits until every chromosome is bioriented.

Once all kinetochores attach, Cdc20–APC/C ubiquitinates securin and cyclin B. Securin destruction frees separase, which cuts cohesin so sisters move apart; cyclin B destruction lowers Cdk1 activity so chromosomes decondense, nuclear envelopes reform and cytokinesis can occur. In animal cells, an actin–myosin II contractile ring pinches the cell in two at the former metaphase plate; in plant cells, Golgi vesicles fuse into a cell plate. Positive feedback between Cdk1, Cdc25 and Wee1 makes mitotic entry switch-like, and protein destruction makes exit irreversible. Many cancers lose these brakes through mutations in RB, p16 or p53.

Key ideas

• The cycle runs G1 → S → G2 → M, and DNA content moves from 2C to 4C and back.
• Cdks need cyclins, and changing cyclin levels drive each phase.
• Phosphorylation by CAK, Wee1 and Cdc25, plus Cdk inhibitors, fine-tunes Cdk activity.
• Mitogens act through cyclin D–Cdk4/6, Rb and E2F to pass the restriction point.
• p53 and p21 stop the cycle in response to DNA damage.
• The spindle assembly checkpoint delays anaphase until all kinetochores attach.
• APC/C destroys securin (allowing sister separation) and cyclin B (allowing mitotic exit).

Formulas and rules

Common mistakes

• Counting chromatids as chromosomes; chromosome number equals the number of centromeres.
• Thinking Cdk levels oscillate; it is mainly cyclin levels (and Cdk activity) that oscillate.
• Mixing up Wee1 (inhibits Cdk1) and Cdc25 (activates Cdk1).
• Saying cyclin B destruction triggers sister separation; securin destruction does.
• Confusing p53 (DNA damage) with Rb (restriction point) roles, though both restrain G1/S.

Before the test, make sure you can

• Name the phases of the cell cycle and identify DNA content and chromatid numbers in each.
• Calculate phase lengths from cell fractions and cell numbers after doublings.
• Explain how cyclins, Cdks, CKIs and phosphorylation regulate the cycle.
• Describe the Rb–E2F pathway and the restriction point.
• Explain the p53–p21 DNA damage response.
• Describe mitotic stages and the spindle assembly checkpoint.
• Predict outcomes when securin, cyclin B, Wee1 or p53 is mutated.
• Interpret cell fusion, MPF injection and yeast mutant experiments.

Words to know

G0

A non-dividing resting state that cells enter from G1.

Cyclin

A regulatory protein whose levels rise and fall in the cycle and that activates a Cdk.

Cdk

Cyclin-dependent kinase; phosphorylates targets to drive cell cycle events.

MPF

Mitosis-promoting factor, the Cdk1–cyclin B complex.

Wee1

A kinase that inhibits Cdk1 by phosphorylating an inhibitory site.

Cdc25

A phosphatase that activates Cdk1 by removing the inhibitory phosphate.

CKI

A Cdk inhibitor protein such as p16, p21 or p27.

Rb

A tumor suppressor that binds E2F and blocks S-phase gene expression until phosphorylated.

E2F

A transcription factor family that turns on S-phase genes.

Restriction point

The late-G1 point after which a cell is committed to divide without further mitogens.

p53

A tumor suppressor transcription factor that halts the cycle or triggers apoptosis after DNA damage.

Cohesin

A protein ring that holds sister chromatids together until anaphase.

Kinetochore

A protein complex on the centromere that attaches to spindle microtubules.

Spindle assembly checkpoint

A control that blocks anaphase until all kinetochores are properly attached.

APC/C

An E3 ubiquitin ligase that targets securin and mitotic cyclins for destruction.

Separase

A protease that cleaves cohesin to start anaphase.

Contractile ring

An actin and myosin II ring that pinches animal cells in two during cytokinesis.

Sample practice questions

30 more questions like these, from level 1 to 5, are in the practice set.