 The timing and rate of cell division is crucial to normal growth, development, and maintenance of multicellular organisms.

 Frequency of cell division varies with cell type  skin cells sustain a lot of damage - divide frequently throughout life  liver cells retain ability to divide, but keep it in reserve  mature nerve & muscle cells are highly specialized - do not divide at all after maturity

 cell communication = signals  chemical signals in cytoplasm give cue  signals usually mean proteins  activators  inhibitors experimental evidence: Can you explain this?

Evidence of cytoplasmic signals  Fuse M phase with G 1 cell – cell immediately condenses DNA and builds spindle  Fuse S phase with G 1 cell – cell enters S phase

 Checkpoints  Control points where stop and go signals regulate the cycle  Check if key cellular processes have been completed correctly  Signals may be internal or external  Generally STOP that must be over ridden by GO

 3 major checkpoints:  G 1  can DNA synthesis begin?  G 2  has DNA synthesis been completed correctly?  M phase  can sister chromatids separate correctly?

 G 1 checkpoint is most critical  restriction point  if cells receives go-ahead signal, completes cell cycle & divides  if does not receive go-ahead signal, cell exits cycle & switches to a non-dividing state called G 0 phase  Most cells are in G 0 phase

 Rhythmic fluctuations of key molecules function as the cell cycle “clock”  2 main types: kinases and cyclins  Kinases - enzymes that activate or deactivate other proteins by phosphorylating them  Cyclins are proteins that combine with kinases

 cyclin and Cdks combine to form MPF, M-phase promoting factor; MPF phosphorylates a variety of proteins and initiates many events of mitosis such as destruction of the nuclear envelope and condensation of chromosomes  Cdk levels are constant throughout the cell cycle but cyclin synthesis rises during S and G 2 phases  MPF activity peaks at metaphase – MPF activates a molecule that destroys cyclin

 cyclin and Cdks combine to form MPF,  M-phase promoting factor  MPF phosphorylates a variety of proteins which initiates many events of mitosis, ex. destruction of nuclear envelope and condensation of chromosomes  Cdk levels are constant throughout the cell cycle but cyclin synthesis rises during S and G 2 phases  MPF activity peaks at metaphase – MPF activates a molecule that destroys cyclin

 Signals that promote cell growth & division  proteins  internal signals  “promoting factors”  external signals  “growth factors”

 Promoting factors  Cyclins  proteins whose concentrations fluctuate in the cell  CDKs  cyclin-dependent kinases  MPF  maturation (mitosis) promoting factor  APC  anaphase promoting complex

 Growth factors  external signals  protein signals released by body cells that stimulate other cells to divide  density-dependent inhibition  crowded cells stop dividing  anchorage dependence  to divide cells must be attached to a substrate

 EXAMPLE: Platelet derived growth factor (PDGF)  made by platelets (blood cells)  binding of PDGF to cell receptors stimulates division and wound begins to heal

 Cancer cells have escaped cell cycle controls  cancer cells are free of both density-dependent inhibition & anchorage dependence  Noncancerous cells grown in culture stop dividing when they touch each other and the sides of the container

 Cancer cells divide excessively & invade other tissues  free of body’s control mechanisms  breakdown in cell cycle control system  breakdown in signaling pathway  cancer cells manufacture their own growth factors  stimulate cell division  stimulate blood vessel growth

 Cancer cells divide indefinitely if have continual supply of nutrients  nearly all normal mammalian cells divide times under culture conditions before they stop, age & die  cancer cells may be “immortal”  HeLa cells from a tumor removed from a woman (Henrietta Lacks) in 1951 are still reproducing in culture

 The abnormal behavior of cancer cells begins when a single cell in a tissue undergoes a transformation that converts it from a normal cell to a cancer cell  usually immune system recognizes & destroys transformed cells  cells that evade destruction proliferate to form a tumor, a mass of abnormal cells

 Benign tumor  abnormal cells remain at originating site as a lump  most do not cause serious problems and can be removed by surgery

 Malignant tumors  cells leave the original site  impair the functions of one or more organs  chromosomal & metabolic abnormalities  lose attachment to nearby cells & are carried by the blood & lymph system to other tissues  start more tumors = metastasis

 Treatments target rapidly dividing cells  high-energy radiation & chemotherapy with toxic drugs

 CHEMICALS  HIGH ENERGY RADIATION  VIRUSES  INHERITED DEFECTS