The Cell Cycle

Overview – The Cell Cycle

The cell cycle is the fundamental process through which all eukaryotic cells grow, replicate their DNA, and divide into genetically identical daughter cells. It underpins tissue growth, repair, and maintenance throughout life. In this article, we’ll explore the key phases of the cell cycle, the molecular control systems that regulate it, and the checkpoints that safeguard genomic integrity. Dysregulation of the cell cycle is a hallmark of cancer, making this topic clinically and academically crucial for final-year medical students.

Definition

  • The cell cycle is the ordered sequence of events that a cell undergoes to duplicate its contents and divide
  • Grounded in the cell doctrine: “All cells arise from pre-existing cells”
  • Ensures faithful transmission of genetic and cytoplasmic material to daughter cells

Functions of the Cell Cycle

  • Accurate replication and inheritance of DNA
  • Equal distribution of chromosomes
  • Coordination of cellular growth with division
  • Maintenance of cell size and content across generations
  • Prevention of mutations and chromosomal errors

Phases of the Cell Cycle

Interphase

  • Majority of the cell’s time is spent here
  • Metabolically active: gene transcription, protein synthesis, and growth

1. G1 Phase

  • Growth phase
  • Duplication of cytoplasmic organelles
  • Prepares for DNA synthesis

2. S Phase

  • Synthesis phase
  • DNA replication occurs
  • Includes the restriction (commitment) point: cell commits to full cycle

3. G2 Phase

  • Further growth and preparation for mitosis
  • Chromosomes begin to condense

4. M Phase (Mitosis & Cytokinesis)

  • Divides the nucleus and cytoplasm
  • Five stages:
    1. Prophase: Chromosomes condense
    2. Prometaphase: Nuclear envelope breaks down; spindle attaches
    3. Metaphase: Chromosomes align at equator
    4. Anaphase: Chromatids separate and move to poles
    5. Telophase: Nuclear envelopes reform; chromosomes decondense
    6. Cytokinesis: Cytoplasm divides, forming two daughter cells

G0 Phase

  • Cells that exit the cycle (e.g. neurons) and do not divide
4 Phases of the Cell Cycle
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Cell-Cycle Control System

  • Complex network of proteins monitors and controls cycle progression
  • Functions as a molecular “checkpoint” system
  • Ensures accurate replication and segregation of DNA
  • Responds to intracellular and extracellular signals
  • Malfunction leads to genomic instability and cancer
The Cell Cycle Control System
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Key Regulatory Molecules

Cyclins and Cyclin-Dependent Kinases (Cdks)

  • Cyclins: regulatory proteins without enzymatic function
  • Cdks: require binding to cyclins for activation
  • Fully activated by Cdk-activating kinase (CAK)
  • Specific complexes trigger different phases:
    • S-Cdk → Initiates S Phase
    • M-Cdk → Initiates M Phase
  • Inactivation: Ubiquitin-mediated proteolysis degrades cyclins
‘Molecular Brakes’ of the Cell Cycle
Rob Hurt, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons

Cell Cycle Checkpoints

G1 Checkpoint

  • Assesses DNA integrity and external signals
  • S-Cdk is inhibited by a Cdk inhibitor if DNA is damaged
  • Prevents progression into S Phase
the cell cycle: G1 Checkpoint- DNA damage prevents S-Phase Entry
https://digitalcommons.olivet.edu/cgi/viewcontent.cgi?article=1102&context=honr_proj

Key Regulators:

  • Cdc6: binds to Origin Recognition Complex (ORC) to suppress replication
    • Phosphorylated and removed by active S-Cdk → DNA replication proceeds
the cell cycle: Cdc6
Source: https://slideplayer.com/amp/7695798/
  • Rb Protein: blocks transcription of S-phase genes
Rb-protein
Rb-protein
1. Source: https://slidetodoc.com/growth-factors-and-enzymelinked-receptor-signal-systems-lecture/
2. Source: https://slidetodoc.com/growth-factors-and-enzymelinked-receptor-signal-systems-lecture/

G2 Checkpoint

  • Ensures complete and correct DNA replication
  • M-Cdk activated only if DNA is undamaged
    • Activated by phosphatase Cdc25
    • Feedback loop enhances activation and suppresses inhibitors
the cell cycle: G2 Checkpoint
Source: https://cdn.technologynetworks.com/ep/pdfs/cell-cycle-regulation-1.pdf

Centrosomes & Spindle Checkpoint

  • Centrosomes = Microtubule organising centres with centrioles
  • Assemble mitotic spindle for chromosome separation
The Centrosomes
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons
  • Spindle checkpoint prevents progression until all chromosomes are attached
    • Cohesin holds chromatids together
    • Once tension is detected → cohesin cleaved → anaphase begins
The Centrosomes
The Centrosomes
1. Source: http://tbl.med.yale.edu/cell_growth_control/reading.php
2. Source: http://tbl.med.yale.edu/cell_growth_control/reading.php
The Centrosomes
A Homologous Pair of Chromosomes with their Attached Sister Chromatids The red and blue colours correspond to a homologous pair of chromosomes. Each member of the pair was separately inherited from one parent. Each chromosome in the homologous pair is also bound to an identical sister chromatid, which is produced by DNA replication, and results in the familiar “X” shape.
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Mitosis – Cellular Division

  • Process of dividing the nucleus and cytoplasm:
    1. Prophase: Chromosomes condense
    2. Prometaphase: Spindle fibres attach
    3. Metaphase: Chromosomes align
    4. Anaphase: Chromatids separate
    5. Telophase: New nuclei form
    6. Cytokinesis: Two daughter cells produced
the cell cycle: Mitosis
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Meiosis – A Side Note

  • Shares mechanisms with mitosis
  • Occurs in gamete production (sperm and ova)
  • Covered in Reproductive Health
Meiosis
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Summary – The Cell Cycle

The cell cycle is the orchestrated process that governs cell replication, ensuring genetic fidelity and balanced cell numbers. Understanding the phases, checkpoints, and regulatory proteins like cyclins, Cdks, and Rb-protein is vital in both basic biology and clinical pathology. For a broader context, see our Cell Biology & Biochemistry Overview page.

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