Cell Cycle Regulation and Tumor Suppressor Genes

Introduction

• The lecture covers high-yield Step 1 topics including the cell cycle and its regulation.
• Focus on proteins involved such as cyclins, retinoblastoma protein (RB), and p53.
• These proteins are coded by tumor suppressor genes, crucial in cancer prevention.

The Cell Cycle

• Two Major Phases
  • Interphase
  • Mitosis

Interphase

• Subphases:
  • G1 Phase: Cell growth, synthesis of proteins for DNA replication.
  • S Phase: DNA replication.
  • G2 Phase: Preparation for mitosis, synthesis of proteins for cell division.
  • G0 Phase: Non-dividing/resting state (e.g., neurons, muscle cells).

Mitosis

• The stage where the cell physically divides into two identical daughter cells.
• Phases of Mitosis:
  • Prophase: Nuclear envelope breaks down, chromatin condenses.
  • Metaphase: Chromosomes align in the center, microtubules attach.
  • Anaphase: Chromosomes pulled to opposite poles.
  • Telophase: Chromosomes decondense, nuclear envelope reforms.

Importance of Mitosis

• Errors in mitosis can lead to:
  • Inhibition of cell division.
  • Cell death.
  • Genetic mutations (e.g., aneuploidy).

Cell Cycle Checkpoints

• Ensure mitosis only occurs in cells without DNA mutations.
• Key Checkpoints:
  • G1-S Checkpoint: Mediated by cyclin E-CDK2 complex.
  • G2-M Checkpoint: Post-DNA replication errors checked.
  • Spindle Checkpoint: Occurs during mitosis to ensure correct chromosome alignment.

Cyclins and Cyclin-dependent Kinases (CDKs)

• Cyclins: Proteins that regulate cell cycle progression.
• CDKs: Enzymes that, when activated by cyclins, phosphorylate proteins.

Cyclin-CDK Complexes

• Necessary for progression through cell cycle checkpoints.

Tumor Suppressor Genes

• Retinoblastoma Protein (RB)

  • Inhibits excessive cell division.
  • Binds to transcription factor E2F to control cell cycle progression.
  • Mutations lead to diseases like retinoblastoma, bladder cancer, etc.

• p53: The Guardian of the Genome

  • Induces p21 to inhibit cyclin-CDK complexes.
  • Ensures only cells free of DNA errors undergo division.
  • Mutations in p53 found in nearly 50% of all malignant tumors.

Conclusion

• Understanding the cell cycle and its regulation is crucial for comprehending cancer development and treatment strategies.

These notes encapsulate key points on cell cycle regulation, the role of specific proteins, and their association with cancer.