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