Cell Cycle & Apoptosis

Phases, Cyclins, and Checkpoints

• $G_1 \to S \to G_2 \to M$, with $G_0$ as a quiescent exit. After S phase a human cell still has 46 chromosomes but 92 chromatids (4C DNA) — sisters stay joined until anaphase.
• CDKs are constitutive; cyclins oscillate. Cyclin D-CDK4/6 reads growth signals, cyclin E-CDK2 commits to S phase, and cyclin B-CDK1 (MPF) triggers mitosis. Checkpoints guard $G_1/S$ (DNA damage), $G_2/M$ (complete replication), and spindle assembly.

Cancer Logic

• Oncogenes (Ras, Myc, HER2) are gain-of-function and dominant; tumor suppressors (p53, Rb, BRCA1/2) require two hits. p53 activates p21 to arrest the cycle or Bax to trigger apoptosis; Rb sequesters E2F until phosphorylated by CDK4/6.
• The APC/C ubiquitinates securin and cyclin B, releasing separase to cleave cohesin and start anaphase.

Apoptosis vs. Necrosis

• Intrinsic pathway: stress opens Bax/Bak pores, cytochrome c escapes, the apoptosome activates caspase-9. Extrinsic pathway: FasL or TNF activates caspase-8. Both converge on executioner caspase-3.
• Apoptosis is orderly and ATP-dependent — a 180 bp DNA ladder, phosphatidylserine "eat me" signals, no inflammation. Necrosis ruptures the membrane and inflames. Bcl-2 overexpression blocks apoptosis in lymphoma.

Key Takeaways

• MPF drives mitotic entry; APC/C ends it.
• p53 loss removes both arrest and apoptosis — the most mutated gene in cancer.
• Ladder plus intact membrane means apoptosis; smear plus lysis means necrosis.