Memories of mitosis: Molecular mechanism that detects defects during cell division could aid cancer treatment
Every day, our cells are hard at work multiplying. Cell division is a precise process, but sometimes this process is impaired and diseases like cancer occur. Mitosis is one of the most important phases in the cell cycle. ...
Prof. Franz Meitinger, head of the Cell Proliferation and Gene Editing Unit at the Okinawa Institute of Science and Technology (OIST), Dr. Hazrat Belal, a researcher at the unit, and their collaborators at the University of California, San Diego, have found a molecular mechanism that prevents multiplication of potentially dangerous cells by measuring the duration of mitosis.
They have shown in their paper published in Science, that this mechanism—the Mitotic Stopwatch Complex—gets stronger with time as cells divide, leading to the removal of abnormal cells to protect the organism.
The Mitotic Stopwatch Complex
Normally, when a cell divides, it makes exact copies of its chromosomes—thread-like structures containing DNA which carries genetic information—and each of the new daughter cells receives a perfect copy. However, sometimes one cell might get too many chromosomes and the other might not get enough, a phenomenon known as "chromosome missegregation."
Mitosis usually takes around 30 minutes to complete, but when cells have a defect, they need more time to organize the chromosomes and segregate them to the daughter cells. This delay results in what the researchers have called the Mitotic Stopwatch—a complex that forms when the cells experience unusual, prolonged mitosis.
Cells can measure how long they spend in mitosis. If mitosis is prolonged due to problems during chromosome separation, the Mitotic Stopwatch Complex is formed, which may lead to cell arrest or cell death. Credit: OIST
The Mitotic Stopwatch Complex remains stable through successive cell cycles, triggering gene expression in both daughter and granddaughter cells. Over time, this signal accumulates and eventually leads to cell arrest or cell death. Credit: OIST
During an extended mitosis PLK1 triggers the formation of a Mitotic Stopwatch Complex that stabilizes and activates the tumor suppressor p53. This complex accumulates during one or successive prolonged mitoses and ultimately causes cell arrest or cell death. Credit: Meitinger et al., 2024
Cancer cells (visualized with FUCCI cell cycle marker in magenta and green) that retain an active Mitotic Stopwatch are vulnerable to anti-mitotic drugs. Credit: Meitinger et al., 2024