Overview
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Mitosis is the process by which an existing cell produces two exact genetic replicas. For this to occur, mitotic chromosomes, each containing a pair of identical sister chromatids, must be divided properly into two daughter cells. Segregation of chromosomes occurs on the mitotic spindle, a complex apparatus that consists of a dynamic array of microtubules and requires the function of numerous proteins at centrosomes, kinetochores, and along spindle microtubules.
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It is essential that chromosome segregation is carried out correctly during every cell division because errors in this process can generate aneuploid cells, in which cells have too many or too few chromosomes. This can be catastrophic, as aneuploidy is well known for causing birth defects (such as Down or Turner syndrome) and is the leading cause of miscarriage and still birth in humans. In addition, aneuploidy is the single most common hallmark of all cancer cells and has been implicated in both the initiation and progression of human tumors.
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As a cell enters mitosis, the two centrosomes separate to opposite sides of the cell to form the two spindle poles, which nucleate dynamic microtubules. Chromosomes attach to spindle microtubules via their kinetochores, which are large proteinaceous structures located at the primary constriction, or centromere region. The kinetochore region is where persistent but dynamic attachments must be made to microtubules and maintained throughout mitosis to allow for chromosome alignment at the metaphase plate and segregation to the two opposite spindle poles in anaphase. Many proteins contribute to the formation of the kinetochore and the generation and regulation of kinetochore-microtubule attachments (some of the proteins are listed in the schematic).
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In order for chromosome segregation to occur correctly, each of the two sister kinetochores on each of the two sister chromatids must become attached to microtubule bundles from opposite poles to become bi-oriented (“amphitelic” attachments). Errors in attachment occur frequently in normal mitotic cells during the process of chromosome alignment. For example, a single kinetochore on a chromosome pair may attach to one pole, while the other kinetochore remains unattached (“monotelic). Or, both sister kinetochores may become attached to the same pole. These chromosomes are referred to as “syntelic.” Other chromosomes may become “merotelic,” in which one kinetochore is attached to microtubules from both poles. Most cells are able to correct these errors in attachment prior to anaphase and subsequent cell division. If errors are left uncorrected, however, a likely outcome for these cells is aneuploidy.

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