Mitosis = eucaryote nuclear division
(Procaryote division is simpler, but different; and we won't cover 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; 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; the signals that control location of the actin-myosin ring come from the poles of the spindle; 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
when cells don't look as if anything particular were going on.
M = mitosis
(labeled with radioactive isotopes) The mechanisms that control the cell cycle:
cyclin dependent kinases (Nobel Prize 2001)
KINASEPhosphates 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,
The particular kinases that control the cell cycle bind specifically to another kind of protein called "cyclins". 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 G2-M checkpoint the metaphase-anaphase checkpoint
2) Loss of control of cell locomotion (also caused by mutations)
They grow without control, without upper limit; broken checkpoints 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:
# slower growing cells, which for some reason can't halt growth while the poisons are around?
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?
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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