Researchers Identify Molecular Stop Signal in Cell Division Monitoring

Many million cells divide throughout the body every second. During nuclear division (mitosis), the genetic material must be divided correctly and fully amongst daughter cells; faults in this process can result in improper development or genetic diseases, and many cancer cells have an uneven number of chromosomes.

As a result, if problems in the division process are detected, the cell has the ability to stop it. Biologists at the University of Duisburg-Essen were able to understand this mechanism at the molecular level. The findings were reported in the scientific journal Current Biology.

Mitotic spindles arise during cell division, which are small fibers that begin at opposing poles of the cell and attach to the chromosomes, pulling one representative of each sister chromatid into one of the two new cells. A robust monitoring system is in place to avoid mistakes during cell division.

This mechanism transmits a ‘Stop! Don’t divide yet!’ signal to the cell if not all chromosomes are properly linked to the mitotic spindle.

Researchers from the University of Duisburg-Essen (UDE) and colleagues from the Max Planck Institute of Molecular Physiology in Dortmund have gained fresh insights into the surveillance system's basic function. They identified how the initiator of the stop signal, a protein kinase called Mps1, is linked to the chromosomal attachment point and only dislodges after the chromosomes are properly connected to the mitotic spindle.

The study, conducted in the Collaborative Research Centre 1430 Molecular Mechanisms of Cell State Transitions at the UDE, solves long-standing issues concerning the mechanism of the molecular stop signal and how it is turned off.

We were able to establish that Mps1 is involved in other processes of chromosome division in addition to the initiation of the stop signal. In future, the mutants we have established could be used to investigate further aspects that are still poorly understood.”

Richard Pleuger, Study First Author, Molecular Genetics I, University of Duisburg-Essen

Predictions of atomic protein structures and binding surfaces utilizing artificial intelligence (AI) were critical to the project. In the future, AI-inspired, precise tests promise to reveal much more about the mechanics of cell division, such as how defective attachments are identified and fixed.