283, Niikura et al. document a new way for abnormal cells to kill themselves. The mechanism might weed out potentially cancerous cells in which the spindle checkpoint has malfunctioned.
Before progressing through mitosis, cells verify that the microtubules of the spindle apparatus are properly attached to the chromosomes. If they aren't, the spindle checkpoint kicks in, halting mitosis to permit repairs. If the spindle checkpoint goes awry, cells can amass extra chromosomes and become cancerous. Apoptosis disposes of many of these aneuploid cells during the next G1 phase. Niikura et al. wanted to find out whether spindle checkpoint defects can also trigger cells to die during mitosis.
The researchers used RNAi to cut cells' output of the checkpoint protein BUB1. Three drugs that disrupt the kinetochore–microtubule connection spurred these cells to expire during mitosis. Like victims of apoptosis, BUB1-deficient cells harbored fractured DNA. However, their demise didn't involve caspase enyzymes, suggesting that this type of cell suicide—which the researchers dubbed caspase-independent mitotic death (CIMD)—is distinct from apoptosis. CIMD doesn't depend on p53, which prompts cells with DNA damage to take their own lives, but does require its cousin p73. The results indicate that cells have a mitotic self-elimination mechanism in case the spindle checkpoint falters. Some details of CIMD remain mysterious, however. For example, the researchers are now investigating why CIMD can occur if BUB1 levels are low, but not if the protein is altogether absent.