Mechanism of chromosomal instability

Chromosomal instability (CIN), or the tendency to lose or gain whole chromosomes, is a hallmark of cancerous cells. These series of animations illustrate how CIN occurs in cells with multiple centrosomes.

In normal cell division, the two centrosomes, which are located at opposite poles, each attach to the kinetochore of one of the two chromatids of a chromosome. As cell division progresses, the sister chromatids are pulled apart and segregate to different daughter cells. It is also possible, however, for centrosomes at different poles to attach to the same kinetochore, creating what's known as a merotelic attachment. These merotelic attachments, if not fixed quickly enough, can result in lagging chromosomes and the formation of micronuclei.

In cells with multiple centrosomes, a multi-polar spindle is often formed. In many cases, these spindles resolve into bipolar spindles and undergo cell division. Depending on how the kinetochore attachments were made and how the centrosomes segregate, this may result in having one or more merotelic chromosomes. In the case where two centrosomes at the same pole attach to a single kinetochore (known as a syntelic attachment), chromosome segregation proceeds as normal.

Published as a supplemental figure in:

Ganem NJ, Godinho SA, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature 2009 Jul 9;460(7252):278-82.

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Cell division with normal chromosome segregation
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Cell division with merotelic and syntelic attachments
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Many thanks to David Pellman and Neil Ganem (Harvard Medical School) for collaborating on this project.

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This work by Janet Iwasa is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.