Researchers at Hokkaido University report that cells left with an extra set of DNA after a division error can have markedly different outcomes depending on how the division fails—findings that could help explain why some abnormal cells persist in diseases where whole-genome duplication is common, including cancer.
Scientists have long linked whole-genome duplication (WGD)—when a cell ends up with double the usual amount of DNA—to harmful outcomes such as cellular dysfunction and genetic instability. A new study from Hokkaido University argues that the mechanism that produces WGD is a major factor in what happens next.
The researchers compared two common routes to WGD:
- Cytokinesis failure, in which the cell completes most steps of mitosis but fails at the final physical split into two cells.
- Mitotic slippage, in which the cell exits mitosis too early, before chromosomes are properly separated.
Using live-cell imaging and chromosome-labeling approaches, the team found that cells produced through cytokinesis failure were generally more stable and more likely to survive, while cells produced through mitotic slippage more often showed uneven chromosome distribution and lower survival.
The study also reports that experimentally improving chromosome separation in cells undergoing mitotic slippage made those cells significantly more viable, pointing to chromosome organization and segregation as a key driver of these different fates.
The findings may carry implications for cancer research, the authors note, because whole-genome duplication is commonly observed in cancer cells and can be triggered unintentionally by some therapies—raising the possibility that the cells most likely to persist after WGD could help fuel continued growth or recurrence.
The work was published in Proceedings of the National Academy of Sciences by Masaya Inoko, Guang Yang, Yuki Tsukada and Ryota Uehara.
