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Cell Cycle and Mitosis

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Cell Cycle Stages in growth & division G1 Phase S Phase G2 Phase M Phase Cytokinesis copyright cmassengale

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G1 Phase First growth stage Cell increases in size Cell prepares to copy its DNA copyright cmassengale

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Synthesis Phase Copying of all of DNAs instructions Chromosomes duplicated copyright cmassengale

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G2 Phase Time between DNA synthesis & mitosis Cell continues growing Needed proteins produced copyright cmassengale

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M Phase Cell growth & protein production stop Cells energy used to make 2 daughter cells Called mitosis or karyokinesis (nuclear division) copyright cmassengale

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The Cell Cycle Most of the cell's life is spent doing its regular function.Most of the cell's life is spent doing its regular function. Cells divide along a rough time frame called its Cell Cycle.Cells divide along a rough time frame called its Cell Cycle. The Cell cycle consists of the folowing steps:The Cell cycle consists of the folowing steps: G1 (Gap 1) Phase - Cell performs its normal function (cells which do not divide stay in this stage for their entire life span)G1 (Gap 1) Phase - Cell performs its normal function (cells which do not divide stay in this stage for their entire life span) S (Synthesis) Phase - Here the cell actively duplicates its DNA in preparation for divisionS (Synthesis) Phase - Here the cell actively duplicates its DNA in preparation for division G2 (Gap 2) Phase - Amount of cytoplasm (including organelles) increases in preparation for division.G2 (Gap 2) Phase - Amount of cytoplasm (including organelles) increases in preparation for division. Mitosis - Actual division occursMitosis - Actual division occurs

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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

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Checkpoint control system 3 major checkpoints: G 1 /S can DNA synthesis begin? G 2 /M has DNA synthesis been completed correctly? commitment to mitosis spindle checkpoint are all chromosomes attached to spindle? can sister chromatids separate correctly?

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Growth Factors and Cancer Growth factors can create cancers proto-oncogenes normally activates cell division growth factor genes become oncogenes (cancer-causing) when mutated if switched ON can cause cancer example: RAS (activates cyclins) tumor-suppressor genes normally inhibits cell division if switched OFF can cause cancer example: p53

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Cancer & Cell Growth Cancer is essentially a failure of cell division control unrestrained, uncontrolled cell growth What control is lost? lose checkpoint stops gene p53 plays a key role in G 1 /S restriction point p53 protein halts cell division if it detects damaged DNA options: stimulates repair enzymes to fix DNA forces cell into G 0 resting stage keeps cell in G 1 arrest causes apoptosis of damaged cell ALL cancers have to shut down p53 activity p53 discovered at Stony Brook by Dr. Arnold Levine p53 is the Cell Cycle Enforcer

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DNA damage is caused by heat, radiation, or chemicals. p53 allows cells with repaired DNA to divide. Step 1 DNA damage is caused by heat, radiation, or chemicals. Step 1 Step 2 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Step 3 p53 triggers the destruction of cells damaged beyond repair. ABNORMAL p53 NORMAL p53 abnormal p53 protein cancer cell Step 3 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. Cell division stops, and p53 triggers enzymes to repair damaged region. Step 2 DNA repair enzyme p53 protein p53 protein p53 master regulator gene

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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 It s like an out-of-control car with many systems failing!

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What causes these hits? Mutations in cells can be triggered by UV radiation chemical exposure radiation exposure heat cigarette smoke pollution age genetics

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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 tumor 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

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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

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New miracle drugs Drugs targeting proteins (enzymes) found only in cancer cells Gleevec treatment for adult leukemia (CML) & stomach cancer (GIST) 1st successful drug targeting only cancer cells Novartes without Gleevec with Gleevec

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Cell Division Mitosis

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Mitosis Eukaryotes divide by a more complicated system called MitosisEukaryotes divide by a more complicated system called Mitosis This is because:This is because: 1.They have a nucleus which must be broken up and then reformed 2.They have their DNA packaged in the form of Chromosomes 3.Chromosomes are composed of Chromatin 1.Made of DNA Strands & Proteins 4.Also contain Nucleosomes containing Histones - Proteins the DNA is wrapped around Name for the DNA/Protein complex is Chromatin 5.They usually have more than 1 chromosome (Humans have 23 pairs) 6.They have numerous organelles to equally share

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Chromatin / Chromosomes

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Interphase Cell Replicates its DNA/Chromosomes in preparation of upcoming divisionCell Replicates its DNA/Chromosomes in preparation of upcoming division Animal Cell Plant cell

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Mitosis is a continuum of changes. For description, mitosis is usually broken into 4 subphases: prophase, metaphase, anaphase, and telophase. Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings

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By late interphase, the chromosomes have been duplicated. The centrosomes begin to organize microtubules into an aster (star). Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5a

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In prophase, the chromatin condenses into chromosomes. The chromosomes are two identical threads (sister chromatids) joined at the centromere. Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5b

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During late prophase, the nuclear envelope fragments. Microtubules from the spindle interact with the chromosomes. Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5c

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Metaphase chromosomes gather at the midline of the cell with their centromeres aligned on the metaphase plate. Enzymes separate the Sister chromatids. Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5d

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At anaphase, the centromeres divide, separating the sister chromatids. Each is now pulled toward the pole to which it is attached by spindle fibers. By the end, the two poles have equivalent collections of chromosomes. Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5e

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At telophase, the cell continues to elongate. Two nuclei begin to form, surrounded by the fragments of the parents nuclear envelope. Chromatin becomes less tightly coiled. Cytokinesis, division of the cytoplasm, begins. Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5f

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Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5 left

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Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.5 right

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Prophase Animal Cell Plant Cell

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Metaphase Animal Cell

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Anaphase

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Telophase (cytokenesis) Animal Cell

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Animal Cytokeneisis With animals, the membranes pinch together to form a Cleavage Furrow, which eventually fuses to form two daughter cells

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Overview of Mitosis

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Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 12.9