Mitosis = eucaryote nuclear division (Procaryote division is simpler, but different; and we won't cover it; if anyone is especially curious, I can tell them more about it.) Stages of mitosis: DNA has already been copied long before cell division, so each chromosome is really a pair of identical copies, that remain stuck to each other until "anaphase "mitosis. Prophase: chromosomes "condense", the DNA becomes compressed together and becoming visible in the microscope. Nuclear membrane disappears; some key proteins get phosphates attached to them (mostly to the OH groups on the side chains of serines) This makes them more soluble, in effect, so they sort of "dissolve" in the cytoplasm. In some lower plants, the nuclear membrane doesn't break down this way, and continues to be there all through cell division) two "poles" move apart, each at the center of an array of microtubules. Each chromosome attaches to microtubules at a special location of the chromosome called the "kinetochore". These microtubules pull each chromatid (=duplicated chromosome) & a tug of war develops with the kinetochore of each chromatid being pulled toward the opposite pole. (Prof Kerry Bloom of the UNC Biology Dept is an expert on kinetochores; and Prof Ted Salmon is the world expert on how microtubules pull on chromosomes is of this department; and I once wrote 2 or 3 papers on how cells divide.) Metaphase: Chromosome pairs are located half way between the poles of the "mitotic spindle" = mitotic apparatus Anaphase: Chromosome pairs separate, and each moves toward a pole. (and opposite poles usually also move further apart) Cytokinesis division of cell into two parts; separation of cytoplasm In animal cells, by formation and contraction of a belt-like ring of actin and myosin. In plant cells, by secretion of a new cell wall across the middle. In animal cells; the signals that control location of the actin-myosin ring come from the poles of the spindle; NOT from the chromosomes or the middle of the spindle. Ray Rappaport's "doughnut experiment". Telophase: nuclei re-form in each cell (which should be separate by now) Mitosis is over. "Interphase" = between one mitosis and the next The cell cycle DNA is copied about half-way through interphase when cells don't look as if anything particular were going on. M = mitosis G1 = "gap 1" or "growth 1" or something. "Gee-One" S = Synthesis of DNA maybe 1/2 hour to 5 or 6 hours G2 = "Gee-Two M, again. The main method for determining the time of S is incorporation of labeled thymidine into DNA (labeled with radioactive isotopes) The mechanisms that control the cell cycle: cyclin dependent kinases (Nobel Prize 2001) "kinase"= an enzyme that specifically bind phosphates to particular different proteins. KINASE some particular protein + ATP -------------> protein-Phosphate Phosphates attach to side chains of serine, threonine and tyrosine which are the only 3 amino acids that have -OH groups Cells have hundreds of different kinases, each specific for a certain protein, or group of proteins. They also have hundreds of a different kind of enzyme, "phosphatases" that cause removal of phosphates back off of proteins The particular kinases that control the cell cycle bind specifically to another kind of protein called "cyclins" for this reason they are called "cyclin dependent kinases" For example, during G1, each cell synthesizes more and more of one of their kinds of cyclins, until enough accumulates to activate kinases There are three (known) checkpoints the G1-S checkpoint the G2-M checkpoint the metaphase-anaphase checkpoint Cancer is caused by 1) Somatic mutations that inactivate controls of the cell cycle and 2) Loss of control of cell locomotion (also caused by mutations) Cancer cells do not grow faster than normal cells They grow without control, without upper limit; broken checkpoints they keep on growing and dividing when normal cells would have been inhibited, and/or when normal cells would have self-destructed Nevertheless, nearly all anti-cancer drugs are designed to poison either DNA synthesis or microtubule formation.   Questions that you should be able to answer about cell division: 1) At what stage of mitosis does the nuclear membrane disappear? 2) What change occurs in the chromosomes at this same time? 3) What sort of biochemical process causes the changes in the properties of proteins associated with the nuclear membrane? 4) Do biochemical changes of this same general kind also occur at other stages of the cell cycle and cell division? 5) What cytoskeletal fibers form connections to chromosomes? 6) What it the name of the specific location on the chromosome which become connected to these cytoskeletal fibers? 7) What is meant by the "mitotic spindle" = "mitotic apparatus"? 8) Where do the chromosomes accumulate during metaphase? 9) The accumulation of chromosomes at this location results from what forces varying in proportion to the distances between what and what? **10) By what experiments (done by UNC Biology students) was it demonstrated that these forces vary according to those rules? 11) What happens in anaphase? *12) Figure out whether the movements of the chromosomes during anaphase can be explained by the same forces that control the position of the chromosomes during metaphase! 13) How can a phosphatase enzyme cause the re-formation of nuclear membranes in the two daughter nuclei in telophase? 14) In cytokinesis, what is the mechanical difference between plant and animal cells. 15) What experimental evidence shows that formation of the contractile ring (in dividing animal cells) is induced to form by signals from the spindle poles, rather than from either the spindle equator or the chromosomes. 16) Chemicals that specifically poison formation of microtubules are often used for what medical purpose? 17) (trick question) During which stage of mitosis are the DNA base sequences copied? (if any?) 18) What is the name of the period of time between the end of one mitosis and the beginning of DNA replication? 19) What is the period of time between the end of DNA replication and prophase of the next mitotic division? 20) Chemicals that damage DNA or poison its replication are used to treat what disease? **21) PLEASE ARGUE PRO OR CON: If a certain chemical prevents cells from some stage of growth and division, A) Then faster-growing cells will be killed by it, but slow growing cells won't be killed? B) Then the chemical should slow or prevent growth, but should kill neither fast-growing nor slow-growing cells? C) Cells should be able to protect themselves from such poisons by stopping or slowing-down their growth as long as the poisons are around? D) Cancerous cells won't be able to slow their growth in response to such poisons? E) Which of the following will be more likely to be killed when treated with poisons of DNA synthesis or of mitosis: # faster growing cells, that CAN halt growth while the poison is around? # slower growing cells, which for some reason can't halt growth while the poisons are around? 22) What are "cell cycle checkpoints"? 23) How many places in the cell cycle are there checkpoints? 24) What could happen if a mutation altered one or more of the proteins whose function is to control one of these cell cycle check-points. *25) Does it make sense that many cancers are caused by particular over-active kinase enzymes? **26) Can you imagine drugs that either prevent or kill cancer cells by attacking just those cells in which a certain kinase is over-active? *27) Which of the following might be useful as new kinds of anti-cancer drugs? a) Chemicals that have nearly the same bond structure as purines or pyrimidines, but differ from normal ones? b) Chemicals that block formation of microtubules? c) Chemicals that block disassembly of microtubules? d) Chemicals that block condensation of DNA in prophase? e) A chemical analog of ATP that blocks kinases? f) A chemical analog of ATP that is converted into a poison when a kinase acts on it?

 

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