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Transcript
Regulation of Cell Division AP Biology 2006-2007 Activation of cell division How do cells know when to divide? cell communication signals chemical signals in cytoplasm give cue signals usually are proteins activators or inhibitors AP Biology Coordination of cell division Multicellular organisms coordinate cell division across different tissues & organs critical for normal growth, development & maintenance coordinate timing of cell division rates of cell division not all cells may have the same cell cycle AP Biology Frequency of cell division Frequency of cell division varies by cell type embryo cell cycle < 20 minute skin cells divide frequently throughout life 12-24 hours cycle liver cells retain ability to divide, but keep it in reserve M metaphase anaphase divide once every year or two prophase mature nerve cells & muscle cells C G2 do not divide at all after maturity permanently in G0 S AP Biology telophase interphase (G1, S, G2 phases) mitosis (M) cytokinesis (C) G1 There’s no turning back, now! Overview of Cell Cycle Control Two irreversible points in cell cycle 1) replication of genetic material 2) separation of sister chromatids Checkpoints process is assessed & possibly halted sister chromatids centromere single-stranded AP Biology chromosomes double-stranded chromosomes Checkpoint control system Checkpoints cell cycle controlled by STOP & GO chemical signals at critical points signals indicate if key cellular processes have been completed correctly 3 major checkpoints: AP Biology G1, G2 and M Checkpoint control system 3 major checkpoints: G1 Can DNA synthesis begin? G2 Has DNA synthesis been completed correctly? Commitment to mitosis M Are all chromosomes attached to spindle? Can sister chromatids separate correctly? AP Biology Major Checkpoints 1. G1 checkpoint (Most important!) Controlled by cell size, growth factors, environment “Go” completes whole cell cycle “Stop” cell enters nondividing state (G0 Phase) 2. G2 checkpoint Controlled by DNA replication completion, DNA mutations, cell size 3. M-spindle (Metaphase) checkpoint Check spindle fiber (microtubule) attachment to chromosomes at kinetochores (anchor sites) AP Biology G1 Checkpoint is the most critical! Primary decision point “restriction point” If cell receives a “GO ahead”signal, it will divide If cell does not receive signal, it exits cycle & switches to G0 phase Apoptosis – cell death AP Biology G1 Checkpoint AP Biology G0 phase G0 phase non-dividing, differentiated state many human cells in G0 phase liver cells M Mitosis G2 Gap 2 S Synthesis AP Biology in G0, but can be “called G1 Gap 1 G0 Resting back” to cell cycle by external cues nerve & muscle cells highly specialized stopped in G0 & can never divide Cell Cycle Control System Checkpoint = control point where stop/go signals regulate the cell cycle AP Biology “Go-ahead” signals Protein molecules that promote cell growth & division internal signals “promoting factors” external signals “growth factors” AP Biology Where is the P attached? “Go-ahead” signals Protein molecules that promote cell growth & division internal signals “promoting factors” external signals “growth factors” Primary mechanism of control: phosphorylation Use of kinase enzymes which either activate or inactivate cell signals by adding a phosphate AP Biology Where is the P attached? Internal Regulatory Molecules • Kinases : protein enzyme controls cell cycle; active when connected to cyclin • Cyclin-dependent kinase: Cdk • Cyclins: proteins which attach to kinases to activate them; levels fluctuate in the cell cycle • When are cyclin levels highest? AP Biology Cyclin & Cyclin-dependent kinases CDKs & cyclin drive cell from one phase to the next in cell cycle proper regulation of cell cycle is so key to life the genes for these regulatory proteins have been highly conserved through evolution AP Biology the genes are basically the same in yeast, insects, plants & animals (including humans) inactivated Cdk Cell cycle Chemical signals Cyclins regulatory proteins levels cycle in the cell phosphorylates cellular proteins activates or inactivates proteins Cdk-cyclin complex Forms MPF complex Triggers movement into next phase AP Biology activated Cdk Internal Regulatory Molecules MPF = maturation-promoting factor • AP Biology specific cyclin-Cdk complex which allows cells to pass G2 and go to M phase External Regulatory Factors AP Biology External Regulatory Factors Growth Factor: proteins released by other cells to stimulate cell division Density-Dependent Inhibition: crowded cells normally stop dividing; cell-surface protein binds to adjoining cell to inhibit growth Anchorage Dependence: cells must be attached to another cell or ECM to divide AP Biology External signals Growth factors coordination between cells protein signals released by body cells that stimulate other cells to divide density-dependent inhibition crowded cells stop dividing When not enough growth factor left to trigger division in any one cell, division stops anchorage dependence to divide cells must be attached to a substrate or tissue matrix “touch sensor” receptors AP Biology Growth factor signals growth factor nuclear pore nuclear membrane P P cell division cell surface receptor protein kinase cascade Cdk P P E2F chromosome P APcytoplasm Biology nucleus M-spindle Checkpoint: Mitotic spindle at metaphase Kinetochore = proteins associated with DNA at centromere AP Biology M checkpoint G2 checkpoint Chromosomes attached at metaphase plate • Replication completed • DNA integrity Active Inactive Inactive Cdk / G2 cyclin (MPF) M Active C cytokinesis mitosis G2 G1 S MPF = Mitosis Promoting Factor AP Biology Cdk / G1 cyclin Active G1 checkpoint Inactive • Growth factors • Nutritional state of cell • Size of cell Cancer & Cell Growth Cancer is essentially a failure of cell division control unrestrained, uncontrolled cell growth What control is lost? gene p53 plays a key role in G1 restriction point p53 protein halts cell division if it detects damaged DNA options: p53 is the Cell Cycle Enforcer stimulates repair enzymes to fix DNA forces cell into G0 resting stage keeps cell in G1 arrest causes apoptosis of damaged cell ALL cancers have to shut down p53 activity AP Biology p53 — master regulator gene NORMAL p53 p53 allows cells with repaired DNA to divide. p53 protein DNA repair enzyme p53 protein Step 1 Step 2 Step 3 DNA damage is caused by heat, radiation, or chemicals. Cell division stops, and p53 triggers enzymes to repair damaged region. p53 triggers the destruction of cells damaged beyond repair. ABNORMAL p53 abnormal p53 protein Step 1 DNA damage is caused by heat, radiation, or AP chemicals. Biology cancer cell Step 2 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. Step 3 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Development of Cancer Cancer develops only after a cell experiences ~6 key mutations (“hits”) unlimited growth turn on growth promoter genes ignore checkpoints turn off tumor suppressor genes (p53) escape apoptosis turn off suicide genes immortality = unlimited divisions turn on chromosome maintenance genes promotes blood vessel growth turn on blood vessel growth genes overcome anchor & density dependence turn off touch-sensor gene AP Biology It’s like an out of control car! What causes these “hits”? Mutations in cells can be triggered by AP Biology UV radiation chemical exposure radiation exposure heat cigarette smoke pollution age genetics Tumors Mass of abnormal cells Benign tumor abnormal cells remain at original site as a lump p53 has halted cell divisions most do not cause serious problems & can be removed by surgery Malignant tumors cells leave original site lose attachment to nearby cells carried by blood & lymph system to other tissues start more tumors = metastasis impair functions of organs throughout body AP Biology Traditional treatments for cancers Treatments target rapidly dividing cells high-energy radiation kills rapidly dividing cells chemotherapy stop DNA replication stop mitosis & cytokinesis stop blood vessel growth AP Biology