The goal is to understand the equal distribution of chromosomes to the daughter cells in mitosis and meiosis. An explanation for the normal success in chromosome distribution would also help explain the failures that result in Down's syndrome and other chromosome diseases in humans. Equal distribution depends upon directed chromosome movement in mitosis. The current explanation of movement in anaphase does not explain congression, the movement of chromosomes in prometaphase to a position midway between the spindle poles. An explanation of congression in terms of forces and mechanics is sought.
The aim i s not only to test current models, but to provide the basis for better models in the future. The plan is to characterize better what actually happens during congression. The forces that produce congression will be measured in absolute units. The possibility of pole-to-chromosome as well as poleward forces will be examined experimentally. Chromosomes in prometaphase commonly spend more time immobile and in contrary movement than in congression. The spindle conditions that underlie these vagaries of chromosome behavior will be characterized by studies of microtubules in living cells by image-enhanced polarization microscopy. Errors in microtubule arrangement that would lead to unequal chromosome distribution are common early in mitosis. The correction of errors by reorientation will be studied by observations of microtubules during reorientation in living and demembranated cells. The proper arrangement of microtubules is stabilized by tension forces. The minimal force required will be measured. The effect of force on microtubules will be determined by micromanipulation of microtubules in vitro. The possibility that tension stabilizes microtubule attachments to the spindle will be tested directly by imposing tension on unstable microtubules.
| King, J M; Hays, T S; Nicklas, R B (2000) Dynein is a transient kinetochore component whose binding is regulated by microtubule attachment, not tension. J Cell Biol 151:739-48 |
