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THE CELL CYCLE IS PRECISELY REGULATED The timing and rate of cell division is crucial to normal growth, development, and maintenance of multicellular organisms. CELL CYCLE FREQUENCY OF CELL DIVISION 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 HOW DO CELLS KNOW WHEN TO DIVIDE? cell communication = signals chemical signals in cytoplasm give cue signals usually mean proteins activators inhibitors experimental evidence: Can you explain this?http://bio.kimunity.com HOW DO CELLS KNOW WHEN TO DIVIDE? Evidence of cytoplasmic signals Fuse M phase with G1 cell – cell immediately condenses DNA and builds spindle Fuse S phase with G1 cell – cell enters S phase CHECKPOINT CONTROL SYSTEM 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 CHECKPOINT CONTROL SYSTEM 3 major checkpoints: G1 can DNA synthesis begin? G2 has M DNA synthesis been completed correctly? phase can sister chromatids separate correctly? G1 CHECKPOINT G1 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 G0 phase Most cells are in G0 phase HOW DOES THE CELL “TELL TIME”? 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 HOW DOES THE CELL “TELL TIME”? 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 G2 phases MPF activity peaks at metaphase – MPF activates a molecule that destroys cyclin HOW DOES THE CELL “TELL TIME”? 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 G2 phases MPF activity peaks at metaphase – MPF activates a molecule that destroys cyclin CDK ALWAYS PRESENT – RISE IN CYCLIN MEANS RISE IN MPF – TRIGGERS MITOSIS DESTRUCTION OF CYCLIN ENDS MITOSIS “GO-AHEAD” SIGNALS Signals that promote cell growth & division proteins internal signals “promoting external factors” signals “growth factors” PROTEIN SIGNALS Promoting factors Cyclins proteins whose concentrations fluctuate in the cell CDKs cyclin-dependent kinases MPF maturation (mitosis) promoting factor APC anaphase promoting complex PROTEIN SIGNALS Growth factors external signals protein signals released by body cells that stimulate other cells to divide density-dependent crowded anchorage to inhibition cells stop dividing dependence divide cells must be attached to a substrate GROWTH FACTORS 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 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 OVERRIDES CHECKPOINTS 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 Cancer cells divide indefinitely if have continual supply of nutrients nearly all normal mammalian cells divide 20-50 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 CANCER 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 TUMORS 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 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 TREATMENT FOR CANCERS Treatments target rapidly dividing cells high-energy radiation & chemotherapy with toxic drugs WHAT CAN CAUSES THE GENETIC CHANGES THAT LEAD TO LOSS OF CONTROL OF THE CELL CYCLE CHEMICALS HIGH ENERGY RADIATION VIRUSES INHERITED DEFECTS