For more than a century, scientists have believed that cells reproduce strictly through the cellular process of cytokinesis during mitosis. But now an entirely new type of cell division process has been discovered, one that may rescue cells from abnormal cell divisions that result in aneuploidy and cancer.
“What we saw in the system we were studying, is that this recovery mechanism was happening about 90% of the time and that the cells were getting abnormal chromosome sets about 10% of the time,” said Burkard.
Burkard and his lab identified the new cellular process when they blocked cells from undergoing cytokinesis—a critical process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells.
“We discovered that in our bodies, if cells miss that step of cytokinesis, they might be able to recover and become completely normal,” explained Burkard. “So, this might be part of the body’s natural defense against cancer starting. If something goes amiss in a normal division, it doesn’t always result in abnormalities because of this recovery mechanism.”
To block cytokinesis, the group generated a population of human retinal pigment epithelial (RPE) cells that would undergo karyokinesis but miss the cytokinesis stage. The first step was to block microtubule polymerization with a chemical called nocodazole in order to gather cells in mitosis. After a mitotic shake-off to eliminate the non-mitotic cells, the team added a chemical called blebbistatin that inhibits the actin-binding protein myosin II, which is essential for cytokinesis.
The team was left with 90% of cells containing two nuclei after mitosis occurred correctly without the cytokinesis process. Burkard’s lab then conducted cloning experiments and further analyzed the population of these binucleate cells using fluorescent time-lapse microscopy.
“To our surprise when we started cloning those cells, they looked like they were generating perfectly normal healthy colonies in many cases,” said Burkard. “When we went so far as to look at the chromosomes in the cells in the colonies, they were completely normal like the original. So, they had somehow recovered.”
Burkard said that a main challenge was proving that their discovery wasn’t simply related to a contamination of normal cells mixed with cells that had missed cytokinesis.
“It was trickier than we had initially anticipated to do that because if you look with a microscope in a normal well, you can’t really see around the edges very well it turns out because of the walls,” explained Burkard. “So, what we did to deal with that was we used some microfluidic devices and we used some optical plates.”
For now, Burkard says his lab plans to see if klerokinesis happens in more complex cellular environments by conducting test using 3-D cultures and microscopy. His lab would also like to uncover the mechanism that triggers klerokinesis.