Mistaken attachments cause cancer-promoting chromosome distribution errors

Some chromosomes are not properly distributed to dividing cells because both of the two newly forming cells try to pull the chromosome their way, a new study says. This appears to be a major source of distribution errors -- errors that often lead to cancer. Dividing cells first duplicate each of their chromosomes, then use a diamond-shaped apparatus called the spindle to pull one copy of each chromosome into each of the two new cells. Edward Salmon (University of North Carolina at Chapel Hill) and colleagues report in the April 30 issue of The Journal of Cell Biology that the most frequent errors in this process resulted from the attachment of one copy of the chromosome to both ends of the spindle. When all the other chromosomes moved into the two new cells, the mistakenly attached chromosome was left behind in the middle of the dividing cell.

Salmon believes that the problem arises because kinetochores, the areas of chromosomes that attach to the spindle, must satisfy conflicting requirements. Kinetochores must be big enough to ensure attachment to at least one side of the spindle, but small enough such that attachment to both sides of the spindle is unlikely. Sometimes this trade-off does not work out.

The cell has a special surveillance mechanism for detecting errors in chromosome attachment. If the cell detects such errors it pauses to correct them before dividing. This system is good at detecting chromosomes that are not attached to the spindle, or chromosome pairs where both members of the pair are attached to the same side of the spindle. The surveillance system probably detects a lack of pulling or tension at the kinetochore, but unfortunately the kinetochores that Salmon studied were being pulled from both sides. Thus this type of error is not detected by the cell, and can easily lead to mistakes in the number of chromosomes distributed to each cell. Such mistakes are commonly a trigger for cancer.

Contact: Edward Salmon, University of North Carolina at Chapel Hill, 919 962-2265, [email protected]