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Cell Cycle Control

phases of cell cycle
  • G0: cell metabolically active but no proliferation
  • aka quiescent phase
  • G1: cell prepares for division
  • S: DNA synthesis
  • G2: cell prepares for mitosis
  • Mitosis: cell divides into 2 daughter cells
• Ensure major events occur at correct times
G1 checkpoint
  • Restriction point to enter S phase
  • Checks for DNA damage & favorable conditions
  • Nutrient availability in yeast; growth factors in humans
  • G1 checkpoint can direct cell into quiescence (G0) if conditions are not favorable
S checkpoint
  • Checks for DNA damage before/during replication
  • Prevents reduplication of DNA
G2 checkpoint
  • Allows entry into mitosis
  • Checks for DNA damage
  • Ensures DNA is duplicated
Spindle-assembly (M) checkpoint
  • During mitosis: allows entry to anaphase
  • Ensures all chromosomes aligned at metaphase plate & attached to spindle
Cyclin-cdk complexes
  • Active cyclin-CDK complexes control passage through checkpoints by phosphorylating other proteins
  • CDK has enzymatic activity, cyclin does not
  • Cyclin concentrations rise gradually throughout interphase --> peak during mitosis
  • Cyclin degraded at end of mitosis by proteasome
CDK active when:
  • Associated with a cyclin
  • Phosphorylated at activation site
  • Dephosphorylated at its 2 inhibition sites
  • Inactive if fully dephosphorylated or phosphorylated
CLINICAL CORRELATIONS
Stomach cells
• Rarely enter G0: rapidly divide
Red blood cells
• Mostly in G0: never divide
Skin fibroblast cells
• Remain in G0 until stimulated to divide