In-depth Notes on the Cell Cycle

Overview of the Cell Cycle

• The cell cycle is an ordered sequence of events involving cell growth and division into two daughter cells.
  • Consists of:
  • Growth
  • DNA replication
  • Nuclear division
  • Cytoplasmic division (Cytokinesis)

Phases of the Cell Cycle

• The cell cycle can be divided into two major phases:
  • Interphase: Prepares the cell for division, encompasses cell growth and DNA replication.
  • Mitotic Phase: Involves separation of DNA and cytoplasm into two cells.
  • Cytokinesis: Division of the cytoplasm into two daughter cells.

Interphase Breakdown

• Interphase has three distinct phases:
  1. G1 Phase (Gap 1):
  • Cell growth, no major noticeable changes.
  • Accumulating materials needed for DNA synthesis (energy stores, nucleotides, proteins).
  1. S Phase (Synthesis):
  • DNA replication occurs.
  • DNA is in the form of chromatin, loosely coiled to allow access for transcription and replication.
  • Results in sister chromatids being joined at the centromere.
  • Centrosomes are replicated to help form the mitotic spindle.
  1. G2 Phase (Gap 2):
  • Final preparations for division, generating energy and gathering proteins needed for cell division.
  • Duplicating organelles for daughter cells and disassembling the cytoskeleton to allow cellular shape changes.

Mitotic Phase Breakdown

• Karyokinesis: Nuclear division, consists of five phases:
  1. Prophase
  2. Prometaphase
  3. Metaphase
  4. Anaphase
  5. Telophase
• Cytokinesis: Follows karyokinesis and is the division of the cytoplasm.

Special Phases

• G0 Phase:
  • Quiescent or non-active phase where cells like neurons enter and do not divide.
• Cells may re-enter G1 from G0 under favorable conditions.

Cell Cycle Duration

• The cell cycle duration varies greatly among cell types:
  • Average in human cells under optimal conditions: 24 hours
  • G1: approx. 9 hours
  • S Phase: approx. 10 hours
  • G2: approx. 4-5 hours
  • Mitotic Phase: approx. 0.5 hours

Regulation of the Cell Cycle

External Regulators:

• Hormones: Such as human growth hormone can trigger cell division.
• Cell Size: Larger cells have a lower surface area to volume ratio, prompting division due to nutrient uptake challenges.
• Cell Crowding: High-density affects growth; cells cultured at 75% confluency to prevent inhibition of growth.

Internal Regulators:

• Checkpoints: Ensure proper cell cycle progression and DNA integrity.
  • G1 Checkpoint: Checks size, energy reserves, and DNA damage before moving to S phase.
  • G2 Checkpoint: Ensures DNA replication has occurred properly and checks for damage before mitosis.
  • Metaphase Checkpoint: Assesses spindle attachment and sister chromatid alignment.

Regulatory Molecules

• Positive Regulators: Drive cell cycle progression.
  • Cyclins and CDKs (Cyclin-Dependent Kinases): Form complexes that activate proteins for progression.
  • CDKs remain steady; cyclin levels fluctuate to regulate progression between phases.
• Negative Regulators: Halt the cell cycle at checkpoints.
  • Examples include:
  • p53: Detects DNA damage, triggers repair or apoptosis if damage is unfixable.
  • p21: Reinforces p53's actions by inhibiting cyclin-CDK activity.
  • Retinoblastoma protein (RB): Monitors cell size and prevents unnecessary progression by inhibiting E2F transcription factor.

Cancer and the Cell Cycle

• Cancer results from uncontrolled cell division due to mutations in proto-oncogenes and tumor suppressor genes:
  • Proto-oncogenes: Normal genes that regulate cell cycle positively; mutations can convert these to oncogenes that promote uncontrolled growth.
  • Tumor Suppressor Genes: Code for negative regulators that, when mutated, fail to stop abnormal cell cycle progression. Mutations in p53 are common in tumors.
• Replication errors during cell division are termed mutations, drastically affecting protein function, potentially leading to cell death or further replication errors.

Conclusion

• It is critical to understand how internal and external signals regulate the cell cycle, as well as the implications of mutations on cell division, cellular health, and disease.