Cell Cycle Control, Checkpoints, and Cancer Biology
Cell Cycle Dynamics
Ordered progression through division
The cell cycle is governed by phase-specific cyclin-CDK activities, checkpoint surveillance, and ubiquitin-mediated protein turnover. Key checkpoints monitor DNA integrity, spindle attachment, nutrient status, and cell size. Transition between states is not merely temporal but regulatory, involving bistable switches and irreversibility created by feedback and proteolysis.
What is the primary function of the spindle assembly checkpoint?
The spindle checkpoint prevents premature chromatid separation until all kinetochores are correctly attached.
Correct answer: To ensure all chromosomes are properly attached to the spindle before anaphase
How do cyclin-dependent kinases contribute to cell-cycle progression?
CDKs act as master regulators whose activity is controlled by cyclins, inhibitors, and phosphorylation.
Correct answer: They phosphorylate target proteins to drive phase transitions and coordinate replication, mitosis, and checkpoint responses.
Cancer as an Evolutionary Process
Hallmarks and clonal evolution
Cancer arises through the accumulation of genetic and epigenetic alterations that confer selective advantages on cell populations. Hallmarks include sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, angiogenesis, invasion, and immune evasion. Tumors evolve under selection, drift, and spatial constraints, producing intratumoral heterogeneity that complicates treatment.
Why is tumor heterogeneity clinically important?
Diverse clones can differ in sensitivity, enabling selection of resistant populations under treatment.
Correct answer: It can create resistant subclones and therapeutic failure
Explain one mechanism by which a tumor suppressor can be inactivated.
Tumor suppressor pathways are frequently disabled by multiple genetic routes.
Correct answer: By loss-of-function mutation, deletion, epigenetic silencing, or loss of heterozygosity.