The cell division monitoring system

Several million cells divide every second in our body. During nuclear division (mitosis), genetic material must be distributed correctly and completely among daughter cells. Errors in this process can lead to faulty developments or genetic disorders, and many cancer cells are also characterized by an unequal number of chromosomes.

Therefore, if errors in the division process become apparent, the cell may stop it. Biologists from the University of Duisburg-Essen were able to elucidate this process at the molecular level. Their findings are published in Current biology.

During cell division, mitotic spindles are formed: tiny fibers that originate from opposite poles of the cell and bind to chromosomes to attract a representative of each sister chromatid into one of the two resulting cells. A sophisticated monitoring system is in place to prevent errors during cell division. This system sends a “Stop!” Don't divide yet! » signal to the cell until all the chromosomes are correctly connected to the mitotic spindle.

Researchers from the University of Duisburg-Essen (UDE) and colleagues from the Max Planck Institute for Molecular Physiology in Dortmund have now been able to gain new insights into the molecular mechanism of this monitoring system.

They discovered how the initiator of the stop signal, a protein kinase called Mps1, is bound to the chromosome attachment site and how it is only dislodged when the chromosomes are properly attached to the mitotic spindle.

The study, carried out at UDE's 1430 Molecular Mechanisms of Cell State Transitions Collaborative Research Center, answers long-standing questions about the mechanism of the molecular stop signal and how it is turned off.

“We were able to establish that Mps1 is involved in other chromosome division processes in addition to the initiation of the stop signal,” explains Richard Pleuger, first author of the Molecular Genetics I research group led by Professor Stefan Westermann. “In the future, the mutants we established could be used to study other aspects that are still poorly understood.”

Predictions of protein atomic structures and binding surfaces using artificial intelligence (AI) were particularly important for the project. In the future, precise AI-inspired experiments promise to better understand the mechanism of cell division, for example to clarify how faulty attachments are recognized and corrected.