The Cell Cycle: Structure, Regulation, and Clinical Relevance

The Cell Cycle

Overview

The cell cycle is the ordered sequence of events that leads to cell growth and division. It ensures the accurate duplication and distribution of genetic material to daughter cells. Regulation of the cell cycle is critical for normal development and prevention of diseases such as cancer.

Genetic Material

Genome and Chromosomes

• Genome: The complete set of genetic information (including all genes and non-coding DNA) in an organism, distributed across chromosomes.

• Chromosomes: Structures composed of DNA and associated proteins (chromatin) that carry genetic information.

• Eukaryotic chromosomes are linear; prokaryotic chromosomes are generally circular.

• Chromatin: The complex of DNA and proteins that forms chromosomes.

Chromosome Structure

Key Features

• Chromosomes are usually found as long, thin chromatin fibers, except after DNA replication when they condense.

• Sister chromatids: The two identical copies of a duplicated chromosome, joined together by proteins called cohesins and most closely at the centromere.

• Arms: The regions of a chromatid on either side of the centromere.

The Cell Cycle Phases

Major Phases

• Interphase: Period of cell growth and DNA replication, subdivided into:

  • G1 phase (First Gap): Cell grows and carries out normal functions.

  • S phase (Synthesis): DNA replication occurs.

  • G2 phase (Second Gap): Further growth and preparation for division.

• Mitotic (M) phase: Includes mitosis (division of the nucleus) and cytokinesis (division of the cytoplasm).

Mitosis

Phases of Mitosis

Mitosis is the process of nuclear division that, together with cytokinesis, produces two genetically identical daughter cells. It consists of five phases:

1. Prophase: Chromosomes condense; sister chromatids remain joined by cohesins; nucleolus disappears; mitotic spindle and asters begin to form; centrosomes move to opposite poles.

2. Prometaphase: Chromosomes condense further; nuclear envelope fragments; kinetochores form at centromeres; kinetochore microtubules attach to kinetochores; nonkinetochore microtubules interact with those from the opposite pole.

3. Metaphase: Chromosomes align at the metaphase plate (an imaginary plane equidistant from the spindle's two poles); centrosomes are at opposite poles.

4. Anaphase: Cohesin proteins are cleaved by separase, releasing sister chromatids; chromatids move to opposite poles via motor proteins; cell elongates as nonkinetochore microtubules lengthen.

5. Telophase: Two nuclei form; chromosomes decondense; spindle microtubules depolymerize.

Cytokinesis

• Division of the cytoplasm, producing two daughter cells.

• In animal cells, cytokinesis occurs by cleavage (pinching of the plasma membrane), mediated by a contractile ring of actin and myosin.

• In plant cells, cytokinesis occurs by formation of a cell plate from vesicles containing cell wall materials.

Binary Fission

Prokaryotic Cell Division

• Prokaryotes divide by binary fission, a process resembling mitosis.

• DNA replication and partitioning of chromosomes occur concurrently with cell enlargement.

• Cytokinesis occurs by pinching of the plasma membrane.

• Mitosis is thought to have evolved from binary fission.

Cell Cycle Control System

Regulation and Checkpoints

• The cell cycle is regulated by a cyclically operating set of molecules that trigger and coordinate key events.

• Checkpoint: A control point where stop and go-ahead signals regulate the cycle.

• Three major checkpoints:

  • G1 checkpoint: Determines if the cell should divide.

  • G2 checkpoint: Checks DNA integrity before mitosis.

  • M checkpoint: Ensures all sister chromatids are attached to spindle microtubules before anaphase.

• G0 phase: A non-dividing state that cells may enter from G1, sometimes reversibly.

Cell Cycle Regulators

• Cyclin-dependent protein kinases (Cdks): Protein kinases active only when bound to cyclin.

• Cyclin: Regulatory protein whose concentration fluctuates during the cell cycle.

• Maturation Promoting Factor (MPF): A cyclin-Cdk complex that triggers passage through the G2 checkpoint into mitosis.

External Factors Influencing Cell Cycle Progression

• Growth factors: Proteins released by certain cells that stimulate others to divide.

• Density-dependent inhibition: Crowded cells stop dividing due to cell-surface protein interactions.

• Anchorage dependence: Most animal cells must be attached to a solid surface to divide.

Cancer and the Cell Cycle

Loss of Cell Cycle Control

• Cancer cells divide continuously and ignore normal regulatory signals.

• Transformation: Conversion of a normal cell into a cancerous cell.

• Benign tumour: Cancer cells with too few mutations to survive at another site.

• Malignant tumour: Cells capable of invading new tissues (metastasis).

• Chemotherapy: Uses drugs toxic to dividing cells (e.g., Taxol, which prevents microtubule depolymerization).

Henrietta Lacks and HeLa Cells

Historical and Ethical Context

• HeLa cells: The first immortal human cell line, derived from cervical cancer cells taken from Henrietta Lacks without her consent in 1951.

• HeLa cells have been essential for biological research worldwide.

• The story of Henrietta Lacks highlights ethical issues in biomedical research, including consent and racial inequities.

• For further reading: The Immortal Life of Henrietta Lacks by Rebecca Skloot.

Summary Table: Key Cell Cycle Checkpoints

Checkpoint	Main Function	Key Question
G1	Determines if cell should divide	Is the environment favorable? Is DNA undamaged?
G2	Checks DNA integrity	Is all DNA replicated? Is DNA undamaged?
M	Checks chromosome attachment to spindle	Are all chromosomes properly attached to the spindle?

Key Equations and Terms

• Genome size: $\text{Genome size} = \text{number of base pairs in all chromosomes}$

• Cell cycle duration: $\text{Total cell cycle time} = \text{G1} + \text{S} + \text{G2} + \text{M}$

Examples and Applications

• Example: If a cell has 6 chromosomes at G1, after S phase it will have 6 chromosomes, each with two sister chromatids (12 DNA molecules).

• Application: HeLa cells are used in cancer research, vaccine development, and cell biology studies.

Consequences of Checkpoint Failure

• Bypassing the G2 checkpoint can lead to:

  • Loss of chromosomes in daughter cells (aneuploidy)

  • Accumulation of mutations, increasing cancer risk

Additional info: For more details, see Chapter 12 of Campbell Biology and supplemental lecture materials.