i3S discovers how cells balance speed and accuracy during cell division
A team of i3S scientists has identified a key mechanism that enables cells to balance two seemingly contradictory processes during cell division: one that delays division to correct errors and another that penalizes divisions that take too long. The discovery, published in the journal Nature Communications, sheds light on how cells strike a balance between speed and accuracy, preventing both the propagation of genetic errors and unnecessary restrictions on cell growth.
Cell division is essential for tissue renewal and the maintenance of life. During this process, chromosomes, which carry genetic information, must be accurately distributed between two daughter cells. Throughout cell division, microtubules (structures resembling tiny ropes) attach to chromosomes through a specific region known as the kinetochore, functioning as “cables” that help pull them toward each daughter cell. To ensure that this distribution occurs correctly, cells rely on a surveillance mechanism known as the Spindle Assembly Checkpoint (SAC), which acts as a “safety brake”: if chromosomes are not properly attached to microtubules, division is delayed until the errors are corrected.
In recent years, however, a second control system has been discovered. This mechanism acts as a “timer” for cell division, keeping track of how long a cell takes to complete mitosis. When division is excessively prolonged, daughter cells inherit a “memory” of that delay and may stop proliferating, thereby preventing the spread of potential errors.
“We knew these two mechanisms existed, but we did not understand how they communicated with each other,” explains Helder Maiato, leader of the research group. “Our work identifies one of the key points of contact between them and shows how cells can determine an optimal time to complete division.”
Kinetochores: the “boxes” cells try to fill
The team discovered that this communication depends on the number of microtubules attached to kinetochores, structures located on chromosomes that serve as attachment sites for the mitotic spindle. Until now, it was believed that only a few attachments were needed to completely switch off the SAC. The new study demonstrates that the process is far more gradual.
Using a simple analogy, Helder Maiato compares kinetochores to boxes that need to be filled: “It was thought that placing just two or three ‘books’ in the box was enough for the cell to consider everything in order. We showed that this is not the case. Cells can proceed with the box only partially filled, but they take longer to complete division.”
This additional delay is precisely the signal that activates the mitotic memory mechanism. As a result, even cells that divide without apparent errors may become marked by having taken too long and lose their ability to continue proliferating.
Implications for cancer
The study also has potential clinical implications. The memory of prolonged divisions depends on the protein p53, one of the most important tumour suppressors known. According to Helder Maiato, around 70% of cancers exhibit alterations in this system, allowing cells with errors to continue proliferating.
The authors suggest that some anti-cancer treatments may act through this mechanism. Rather than immediately killing cancer cells, they delay cell division long enough to activate mitotic memory and prevent the multiplication of daughter cells. The effectiveness of this effect may depend on the functional status of p53 in each tumour.
“A cell cannot divide either too quickly or too slowly,” concludes Helder Maiato. “We have shown that kinetochore occupancy by microtubules is a central variable in achieving that balance. When this balance fails, the cell leaves behind a memory that shapes the future of its daughter cells.”
