MAIN POINTS FROM THE TEXTBOOK

• cell cycle = interphase (G₁ gap phase + S phase + G₂ gap phase) 
                 + M phase (prophase + metaphase + anaphase + telophase + cytokinesis)
• Easy intro http://www.cellsalive.com/cell_cycle.htm   
• The most important points are explained on CD  Activity 8.1 The Cell Cycle  If you understand everything on this activity well enough to answer its quiz questions correctly, you probably have mastered 90% of the content required for this course.  The same material can be mastered by studying pp. 155-168 and Fig. 8.18, p. 170.  The textbook pages explain more of the experimental details than the CD covers.  
• Unless there is a mistake, all your cells are supposed to contain identical sets of genes.  The point of the cell cycle is that each cell first replicates all of its chromosomes (which contain the genes, even in prokaryotes) and then it divides each pair so that the daughter cells have exactly the same genes.
• the basics of its control:   
  • The way the cell cycle is supposed to work is that the cycle stops at each of several checkpoints, described on fig. 8.16, p. 168.   
  • The cycle does not continue beyond each of the three checkpoints unless certain conditions are ready, and the cell "knows" about the readiness when specific biochemical signals are inside the cell.  
  • Science still doesn't know enough about cell cycle checkpoints, and new discoveries will be in the news during the next few years, maybe in time for the next test or the final exam.  This area of research is crucial for treating cancer; so you will need to understand the basic ideas and some of the vocabulary to explain what's happening to friends concerned about cancer.
  • The most important checkpoint signals are called cyclins.  get it?  cell cycle cyclin'?  
  • The best explanation of typical cyclin behavior in your textbook is on Fig. 8.18, p. 170.
    • start with the end of Fig. 8.18b:  to move from the G₁ stage to the S (for synthesis) stage of the cell cycle, the cell must synthesize the S-phase proteins which are needed for the replication of DNA.  A small regulatory protein, called E2F,  is required to turn on the specific genes for the S-phase proteins.  (E2F turns on only these genes.  We'll come back to how to turn on genes in chapter 15.)
    • Normal cells don't have any E2F until then end of the G₁ stage because E2F is tightly bound to another protein, shown in the example on Fig 8.18b as the tumor-suppressor, Rb.  
    • When a phosphate group (P_i) is covalently attached to the Rb protein, the polarity changes Rb's tertiary shape, releasing E2F.
    • A more generalized sequence is described in Fig. 8.18a.  Here you can see that a protein enzyme called a kinase is responsible for activating a target protein (like E2F) by attaching the phosphate ion from ATP.  There are many kinases which activate specific proteins in cells, but in cell cycle control the kinases involved are called cyclin-dependent kinases, because they don't work unless they form a quaternary structure with _____________.
    • Now we see that we can't move to the S phase without the S-phase proteins, which don't appear until E2F turns on their genes.  And we get no E2F until it's released from its protein complex, which must be phosphorylated by a cyclin-dependent kinase, which must have ATP and cyclin.  
    • Cells nearly always have ATP, but cyclins are mostly absent in normal cells except ....  when?
    • In normal cells something has to increase the concentration of cyclin to set in motion all the events which let the cycle move past the G₁ checkpoint. 
    • Similar sequences occur at the G₂ checkpoint, and other events control the M checkpoint.
• Our cells are eukaryotic.  What kinds of critters have prokaryotic cells?   (Prokaryotic cells divide (of course), but not by mitosis==see p. 164)
• If you need to review the stages of mitosis, study CD Activity 8.2 Phases of Mitosis.  On Wednesday's in-class quiz and Test 2, there may be pictures like fig. 8.2 and 8.10; you will have to identify the stages of some cells.
• Cancer is out-of-control cell division.  It's important to remember that mitosis normally produces identical clone cells so that all normal cells have the proper genes for cell cycle control.  Cancer occurs because of mutations in the genes which produce and regulate the various checkpoints, and treating cancer involves chemotherapy disrupting mitosis and/or blocking the cycle at the checkpoints. 
  • If you understand cell cycle control, you understand the basis of the two-hit hypothesis.
  • The "hits" or mutations are diferent for different kinds of cancer; that's why the "cure" for cancer will never work for all kinds of cancers.
  • Read the textbook and try to apply the principles of cell cycle control  to explain cancer and its current and potential future medical treatments.
  • All normal cells have genes for apoptosis ("programmed" cell suicide).  As embryonic structures  develop normally, some cells die to create spaces between tissues or organs or fingers, for example.  If you could find a chemical which works like E2F to turn on the apoptotic genes but only in the tumor cells or the metastatic cells, you could have a cure.  But it's not easy; why? 
• The scientific method in cell cycle and cancer research:  This chapter is packed with experiments.  You should be prepared for a future "open-book" test question on these experiments:  fig. 8.3, fig. 8.11, fig. 8.13,  fig. 8.14, and the cancer research on pp. 169-172.  For an extra quiz grade to replace a bad past or future quiz grade, turn in a Form for Experiment Summaries for ONE of these experiments before the end of the last lab on Thursday.
• Checklist of terms you should be able to apply:  
  • cell cycle = interphase (G₁ gap phase + S phase + G₂ gap phase) 
                   + M phase (prophase + metaphase + anaphase + telophase + cytokinesis)
  • mitosis, meiosis, chromosome, chromatid (DNA molecule), mitotic spindle, centrosomes, kinetochore, cytokinesis, cleavage furrow, cell plate, protein kinase, protein phosphorylation, cyclin, cyclin-dependent kinase (Cdk), cell-cycle checkpoint, malignant tumor, benign tumor, metastasis, growth factors, tumor suppressor
• Preview of quiz, test, and exam questions
  • all pre-quiz and post-quiz questions on CD 8.1 The Cell Cycle
  • Content Review, p. 173: all #1-6
  • Conceptual Review #2, 3, 5, 6, 7
  • Figure Review #1, 2, 3
  • "open-book" experiment summaries for any of these experiments:  fig. 8.3, fig. 8.11, fig. 8.13,  fig. 8.14, and the cancer research on pp. 169-172. 

Some links to new research 

• Professional research http://www.nature.com/celldivision/library/index.html 
• a professional picture http://jbiol.com/content/figures/1475-4924-2-5-1.jpg
• e-mice cancer research and great links to more resources:  http://emice.nci.nih.gov/learning_tools/ 
• To understand the research: 
• cell theory & mitosis: http://vector.cshl.org/dnaftb/7/animation/fs.html
• Cloning 101:  http://vector.cshl.org/cloning.html 
• mitosis micrographs:   mitosis pictures for practicing for the quiz and test 2
• links to more on mitosis

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