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The multiple centrosomes segregate to opposite ends of the cell and the spindles attach to the chromosomes haphazardly. When anaphase occurs in these cells, the chromosomes are separated abnormally and results in aneuploidy of both daughter cells. [2] This can lead to loss of cell viability [3] and chromosomal instability. [4]
A cell during anaphase. Microtubules are visible in green. Stages of late M phase in a vertebrate cell. Anaphase (from Ancient Greek ἀνα-() 'back, backward' and φάσις (phásis) 'appearance') is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell.
Cancer cells have been observed to divide in multiple directions by evading the spindle assembly checkpoint resulting in multipolar mitoses. [78] The multipolar metaphase-anaphase transition occurs through an incomplete separase cycle that results in frequent nondisjunction events which amplify aneuploidy in cancer cells.
Another way cells prevent over-division is that normal cells will also stop dividing when the cells fill up the space they are in and touch other cells; known as contact inhibition. Cancer cells do not have contact inhibition, and so will continue to grow and divide, regardless of their surroundings.
Presence of Aurora B halts metaphase-to-anaphase transition until proper biorientation is achieved. This is demonstrated in Aurora B deficient cells, where inhibition of Aurora B by hesperadin causes the cell to progress from metaphase to anaphase even when there are misaligned chromosomes in the cell. [33] [34]
Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins , including a cullin ( Apc2 ) and RING ( Apc11 ) subunit much like SCF .
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Anaphase-promoting complex subunit 4 is an enzyme that in humans is encoded by the ANAPC4 gene. [5] [6]A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome.