Unraveling the Role of Cyclin B Docking in Regulating Cell Division

Cell division is essential for the survival of all living organisms, from the simplest yeast to complex human beings. This process relies on various mechanisms to ensure that each step occurs in the correct order and that errors are avoided during the creation of new cells.

Preventing such errors is crucial, as they can lead to issues such as tumor formation. A research team at the University of Konstanz, led by Biologist Thomas Mayer, has identified a control mechanism involving a small binding pocket. This pocket enables cyclins of the B type to dock onto substrates, playing a significant role in maintaining the proper sequence of events during cell division.

The Correct Sequence of Events is Key

During cell division, all steps must occur in the correct sequence. Any deviation from this order can result in malformations. Depending on the type of cell and the stage of the process, such malformations can lead to conditions like tumor formation or infertility.

In two studies, we tested whether the docking site on cyclin B – a type of pocket contributes to the correct sequence of events and, if so, what effects it has. By making targeted changes to this docking site, we were able to demonstrate that malformations occur during cell division when the pocket loses its shape and can no longer dock onto the substrate.”

Thomas Mayer, Professor, Molecular Genetics, University of Konstanz

This issue arises from the interaction between cyclins and a kinase. Kinases are enzymes that phosphorylate amino acids in substrates, a crucial step in cell division. The environment surrounding the amino acids also significantly affects how efficiently phosphorylation occurs. If the kinase moves freely within the cell, it primarily phosphorylates amino acids in optimal environments.

However, if cyclin B docks onto substrates via its pocket, then the kinase 'piggybacks' into the spatial proximity of these substrates. This enables the kinase to also phosphorylate amino acids that are in a less ideal environment. Basically, the pocket of cyclin B functions like a Velcro fastener connecting the kinase and the substrate. This, in turn, contributes to the correct sequence of events in cell division.”

Thomas Mayer, Professor, Molecular Genetics, University of Konstanz

No Pocket = No Correct Cell Division

The research team, led by Thomas Mayer, has demonstrated this mechanism in two cyclins from the B group. Cyclin B1 plays a role in mitosis, a type of cell division. The researchers observed how cyclin B1 uses its pocket to dock onto substrates, thereby influencing the kinase's activity.

As a cross-check, we looked at what happens if the pocket on cyclin B1 is either missing or no longer fits. For this, we mutated the pocket and were able to observe that mitosis no longer proceeds correctly.”

Thomas Mayer, Professor, Molecular Genetics, University of Konstanz

This disruption can lead to errors in chromosome separation, causing mitosis to proceed more slowly or incorrectly, which may result in tumor formation.

Cyclin B3, on the other hand, is crucial for meiosis, another type of cell division. It ensures that meiotic division occurs properly, allowing the development of a healthy egg cell. In the study, the researchers intentionally disrupted the process by altering the cyclin B3 pocket, which prevented the egg cell from maturing.

“A faulty pocket on cyclin B3 can therefore be one cause of infertility,” Mayer concluded.

“Researchers already knew that such pockets exist on the cyclins of the B group. However, we have now been able to document, for the first time, how relevant it is for the correct sequence of events in cell division,” Mayer added.

This research provides a foundation for further studies, contributing to a deeper understanding of cellular processes and paving the way for more targeted treatments for various illnesses.