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Metaphase
As a microtubule hooks onto a chromatid’s kinetochore, the microtubule shortens, pulling the chromatid toward the microtubule’s anchor. At the same time, the microtubule attached to the chromatid’s sister begins to pull toward the opposite side of the cell. Because the sister chromatids are still firmly attached by the cohesin complex, a tug of war results that neatly lines up all of the sister chromatids in the cell’s middle.
Mitosis is all about force. “This is anthropomorphizing the process a bit,” says Orr-Weaver, “but the only way sister chromatids communicate during mitosis is by physically touching and ‘feeling’ what the other is doing. And that’s essential for them to get organized properly.”
“The forces on the chromatids are huge, much greater than is needed to move the chromatids through the viscous fluid that fills the cell,” agrees Cheeseman. “That extra force seems to be needed to signal that the kinetochores have attached properly and the chromatids are ready to divide.” If only one of the two sister chromatids is attached to a microtubule, there is no tension on the pair and both are dragged toward one anchor point. This lack of tension signals that something is wrong, and mitosis stops until the problem is fixed.
Anaphase
With the chromatids lined up and each sister attached to opposite anchor points, the cell is ready to split the sisters apart. The cohesin complex holding the centromeres together is cut, releasing these rubber bands. The sisters pull apart from each other, and evenly and synchronously chug toward opposite anchor points. The duplicate copies of the mother cell’s DNA have been divided between the two daughter cells.
For the past five years, the Orr-Weaver lab has focused on how the shugoshin protein MEI-S332 is triggered to fall off or stay on the chromosome. When the protective protein is removed, the cohesin complex at the centromere falls off, and the chromosomes are no longer bound together, allowing the sister chromatids to separate as mitosis continues. However, if there is no shugoshin protein present, the chromosomes cannot stay bound together, and they float apart.
The Orr-Weaver lab found that a protein complex wedged between the stuck-together chromosomes contains an enzyme that adds a phosphate to one part of MEI-S332, keeping the shugoshin protein stuck to the centromere. When a different enzyme adds a phosphate to another part of MEI-S332, the protein falls off.
Telophase
With complete copies
of the mother cell’s DNA at either end of the cell, the cell continues to divide, forming membranes around the two areas of DNA to create the nuclei for the daughter cells. Once inside the nucleus, the DNA decompresses from its highly compacted state. Voila! Mitosis is complete, and the daughter cells enter their interphase periods.
Although cells usually halt mitosis if anything goes awry, such as sister chromatids attached to the same anchor point or a chromatid that is not attached to an anchor point, mistakes sometimes slip through the cracks. “If cells reach telophase with the wrong number of chromosomes, it’s bad news for the cells—they will most likely die,” says Orr-Weaver.
Another possible result is cancer. Genetic screens show that some cancerous cells possess the wrong number of chromosomes, which they will pass down to their progeny. “Identifying all of the proteins in mitosis and knowing their roles will really increase our knowledge of their relevance for cancer,” says Cheeseman.
Getting a grip
for DNA division
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| Illustrations: Tom DiCesare |
During cell division, the cell separates two copies of its chromosomes, a process called mitosis. For the first part of mitosis, the chromosome copies, or chromatids, are held together by the protein cohesin, shown above as spheres. In the middle of the chromatids, a special bundle of cohesin is prevented from falling off by the protective shugoshin protein, represented as a red outline. The rope-like microtubules, indicated by gray lines, tug the chromatids to the center of the cell in metaphase, the mitosis step shown.
This enlargement shows the center of an attached chromatid pair from the diagram above. The microtubules are attached to the chromatids by a protein complex called the kinetochore (green oval). As the microtubules exert tension on the chromatid pair, the chromatids remain firmly attached due to the cohesin and shugoshin proteins. This tension signals to the cell that the chromatids are ready to
split apart.
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