Lecture 18 Mitosis and Cell Cycle

Lecture 18 Mitosis and Cell Cycle - BME 418, Quantitative...

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BME 418, Quantitative Cell Biology Alan J. Hunt Lecture #18: Mitosis III, Cell Cycle I. Ensuring high fidelity operation of a complex structure like the mitotic spindle could be accomplished in two ways. One possibility is that the construction, operation, and timing are subject to very tight tolerances so that the timing, forces, and direction of movements are reproduced nearly exactly during each round of cell division. This is an extremely problematic strategy for several reasons: 1) Small scale means that prominent thermal fluctuations will significantly influence mechanical events. 2) Chemical reactions involving only a few molecules will show significant variance (generally Poisson distributions, variance = mean). 3) Explicitly defining such a complicated structure poses a significant information storage problem. These are also challenges for engineering nanotechnology . Rather than using such a potentially problematic open-loop system, cells monitor key events that serve as "checkpoints". If critical "all-clear" signals are not received, the cell delays progress into the next phase. This type of regulation is particularly important during progression through the cell cycle. One of the most prominent checkpoints occurs at the metaphase to anaphase transition. This "chromosome distribution checkpoint" delays entry into anaphase if chromosomes are not properly oriented. For example, mitosis is delayed if chromosomes are pulled away from the spindle, or if they are improperly oriented so that both kinetochores are bound to the same pole. But what is actually detected, and how?
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BME 418, Quantitative Cell Biology Alan J. Hunt Rieder et al. (1994) measured the average time from nuclear envelope breakdown (NEB) to anaphase, and the average time from biorientation of the last chromosome (that is becoming attached to microtubules emanating from both poles) to anaphase ( Draw) .
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BME 418, Quantitative Cell Biology Alan J. Hunt They found that though the time from NEB to anaphase was quite variable (23-198 minutes), the time from biorientation to anaphase was fairly constant (23 ± 11 minutes). This suggests that anaphase is inhibited by some signal coming from chromosomes that are not bioriented. Presumably when the last chromosome becomes bioriented a “timer” starts, which allows the chromosome sufficient time to move to the metaphase plate
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This note was uploaded on 09/06/2008 for the course BIOMEDE 418 taught by Professor Hunt during the Winter '08 term at University of Michigan.

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Lecture 18 Mitosis and Cell Cycle - BME 418, Quantitative...

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