Each day, hundreds of billions of cells in our body cycle through a period of growth and division. Yet, the critical orchestration of mitosis, when chromosomes are carefully segregated from one parent cell to the next generation of two daughter cells, lasts only about 30 minutes. It is during this crucial period of cell division that things can go awry. Chromosomes can be misdirected, leading to damaged and diseased cells that progress to different types of cancer.
Researchers from the University of California San Diego have now uncovered a key mechanism that keeps track of mitosis timing and takes note when the process takes too long. "This work shows that cells carefully monitor the time taken to execute mitosis and use that as a filter to eliminate potentially problematic cells," said Arshad Desai, senior author of the paper published in Science. "If a cell takes longer than normal to complete mitosis, then daughter cells will know that their mother struggled to execute mitosis and they'll stop dividing as a safety measure."
The researchers discovered that the "stopwatch" is made up of a biochemical pathway that continually surveys the amount of time spent in mitosis. This pathway features a "memory" function that sums up mitosis delays from one generation to the next. Underlying the pathway is a complex of three proteins, including p53, encoded by the most commonly mutated gene in human cancers. Through a series of experiments, the researchers found that the pathway works as a quality control mechanism that "remembers" mitotic time. Even cell divisions that are sequentially delayed by as little as 20 minutes are labeled as risky.
The researchers believe that the crucial 30 minutes of mitotic time could be evolution's solution to quickly getting through a vital but potentially dangerous part of life when cells are vulnerable. Importantly, they demonstrated that the stopwatch mechanism is switched "off" by many types of cancers, effectively allowing them to tolerate aberrant genomes that undergo longer and problematic mitoses.
"Our research suggests that measuring mitosis time is a mechanism that was developed as a way to protect us," added co-author Karen Oegema. "Essentially, it's another tumor-suppression function tied to p53's job to protect against problematic cells."