checkpoint - specific points where cell cycle can be put on hold 

• 2 irreversible points - replication of genetic material, sister chromatid separation
• kinase - adds phosphate
• phosphatase - takes away phosphate
• phosphorylation/dephosphorylation >> activate/deactivate proteins >> drives cell cycle
• cyclin - proteins displaying characteristic patterns of synthesis/degradation like the cell cycle
• cyclin-dependent kinase (Cdk) - enzyme that controls passage through the checkpoints
• multicellular organisms respond to more external signals and use more Cdk’s than unicellular organisms

G1/S checkpoint - main point where the cell decides whether or not to divide 

• links cell division to cell growth
• aka “restriction point” (R point) in animals
• aka “start” in yeasts
• decision to replicate genome >> decision to replicate
• internal signals - nutritional cell state, cell size
• external signals - factors that promote cell growth/division

G2/M checkpoint - point where cell commits to mitosis 

• can halt if DNA not replicated correctly
• M-phase-promoting factor (MPF) - Cdk that works at this checkpoint; sensitive to substances that disrupt DNA
• removal of inhibitor phosphates acts as signal (damaged DNA >> inhibitory phosphorylation of MPF)

spindle checkpoint – makes sure that all chromosomes attached to spindle for anaphase 

• checks to see if all chromosomes are aligned on metaphase plate
• anaphase-promoting complex – transmits signal that removes inhibitors of protease (which destroys the cohesion that holds chromatids together)

growth factors – regulatory signals that stimulate cell division 

• triggers intracellular signaling systems
• platelet-derived growth factor (PDGF) – promotes fibroblast growth
• overrides cellular controls that normally stop cell division
• most cells need combination of different growth factors to totally promote cell division

cancer – uncontrolled cell growth 

• occurs when cell can’t control division
• p53 – gene controlling G1 checkpoint
  • tells cell to kill itself (apoptosis) if DNA damage can’t be repared
  • prevents development of mutated cells
  • mutation in gene allows cancer cells to continue dividing
• oncogenes – genes that can cause cells to be cancerous
• proto-oncogenes – normal cellular genes; becomes oncogenes when mutated
  • can cause growth receptors to continually stay on, even w/o growth factor
  • can mutate proteins involved in signal cascades between receptor and Cdk
• tumor-suppressor genes – normally inhibits the cell cycle, recessive to proto-oncogenes
• retinoblastoma susceptibility gene (Rb) – only needs a single mutated copy to lead to cancer
  • single cancerous cell in retina >> retinoblastoma forms
  • Rb protein – aka “pocket protein,” has binding pockets for other proteins