206. Cell Cycle Checkpoints

Cell Cycle Checkpoints

This simulation models the eukaryotic cell cycle control system, showing how cyclins, CDKs, and checkpoint proteins coordinate cell division and protect against errors and DNA damage.

Cell Cycle Phases

• G1 (Gap 1): Cell growth, preparation for DNA synthesis
• S (Synthesis): DNA replication
• G2 (Gap 2): Growth and preparation for mitosis
• M (Mitosis): Cell division

Cyclin-CDK Complexes

• Cyclin D-CDK4/6: G1 phase, Rb phosphorylation
• Cyclin E-CDK2: G1/S transition, full Rb inactivation
• Cyclin A-CDK2: S phase, DNA replication
• Cyclin B-CDK1: G2/M transition, mitotic entry

Major Checkpoints

• G1 Checkpoint (Restriction Point): Checks growth factors, cell size, DNA integrity
• S Checkpoint: Monitors DNA replication fidelity
• G2 Checkpoint: Verifies complete, undamaged DNA replication
• M Checkpoint (Spindle Assembly): Ensures proper chromosome attachment

Tumor Suppressors

• Rb (Retinoblastoma): Blocks E2F transcription factors; inactivated by phosphorylation
• p53 (Guardian of the Genome): Activated by DNA damage; induces p21 or apoptosis
• p21: CDK inhibitor; blocks cell cycle progression

DNA Damage Response

• ATM/ATR: Damage sensors that activate checkpoint kinases
• CHK1/CHK2: Checkpoint kinases that stabilize p53
• Cell Fate: Repair → continue, or Apoptosis if irreparable