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Research the Literature on your Own
What controls spindle microtubule polymerization? (Hints: check the literature on centrosomes with special attention to an isoform of tubulin called “gamma-tubulin”. Look into the idea that chromosomes too are able to increase the probability of microtubule polymerization by looking up “ran-GTP” and its ability to alter the tubulin-microtubule equilibrium. Look also at recent evidence for kinetochore-mediated initiation of microtubule growth.) When all these facts are in hand, consider the implications of your knowledge for a basic understanding of how the spindle forms. Is the diversity you have now seen the source of fundamental variation in spindle function, or is it just another example of biological diversity on a fundamental process?
How are sister chromatids held together, and how is this connection severed to allow anaphase onset? (Hints: check out the literature on cohesin, but be sure to get more than one point of view, e.g., work from both the Nasmyth and the Koshland labs. Find out how cohesin is removed from the chromosomes at anaphase onset. See if you can link this process with the issues raised above concerning our understanding how a cell decides when to begin anaphase.)
What is the evidence that motor enzymes contribute to the successful formation of the mitotic spindle? (Hints: check out the literature on loss-of-function alleles of motor enzymes in yeasts. Look as studies that use the injection of function-blocking antibodies into living cells. Look at studies carried out in extracts of frog oocytes, where antibodies can be use to deplete a specific spindle component. Look at more recent literature that uses RNA interference to knock down expression of motor genes.) Now compare your results and ask yourself, which kind of data do you think is the most reliable and why. Are the differences you find a result of biological variability or experimental method?
What aspects of the mitotic spindle contribute to the accuracy of chromosome segregation? (Hints: think first about how you would measure mitotic accuracy, then go to the yeast literature (both budding and fission yeasts) to see how it has actually been done. See what you can find about measurements of segregation accuracy in different genetic backgrounds, i.e., when particular spindle components are compromised by mutation. Now think of other ways in which you could compromise spindle action and see if you can find data on the fidelity of chromosome segregation in these different experimental situations.
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