Keeping Chromosomes in Line: The Hidden Role of CENP-E

By: Erika Joy M. Gumboc | Paralogon

Cell division is one of biology’s oldest concepts that was thought to have been fully understood by now. However, scientists at the Ruder Boskovic Institute in Zagreb, Croatia recently discovered a mechanism involving the centromere protein E (CENP-E), a microtubule-binding protein, that shifts our understanding of chromosome behavior. For more than two decades, scientists believed that CENP-E acted as a mechanical motor that pulls chromosomes toward the center of the cell before division. This long-standing textbook definition is challenged by a recent study implying that the protein plays more of a role in the stabilization of the earliest connections between the chromosomes and the microtubules that guide their movement during mitosis.

A screengrab from ‌Wu, J., Maximilian W.D. Raas, Paula Sobrevals Alcaraz, Vos, H. R., Tromer, E. C., Berend Snel, & Geert J.P.L. Kops. (2023). A farnesyl-dependent structural role for CENP-E in expansion of the fibrous corona. ˜the œJournal of Cell Biology/˜the œJournal of Cell Biology, 223(1). https://doi.org/10.1083/jcb.202303007 

‌Accurate chromosome positioning is a significant factor for successful cell division. For each division, identical copies of DNA must be distributed equally to the two daughter cells. Chromosomes attach to spindle fibers through structures called centromeres in order for them to move and align properly before separation – the incorrect formation of said attachments could cause the chromosomes to be improperly segregated, which can lead to genetic imbalances that are primary causes of developmental problems and diseases.

The recent study led by Kruno Vukusic and Iva Tolic shows that CENP-E acts as more of a regulator rather than a mechanical motor. Instead of physically dragging the chromosomes towards the center, the protein aids in the stabilization of the first attachments between chromosomes and microtubules. Once the stable connections are formed, only then will the spindle fibers allow the chromosomes to accurately align at the metaphase plate of the cell.

The study also revealed the influence of other regulatory proteins in this process. For example, Aurora kinases prevent chromosomes from forming incorrect attachments prior to division. While these reduce error, too much of this activity could also restrict chromosome movement. Surprisingly, CENP-E was found to be able to balance these signals by helping chromosomes establish aforementioned stable attachments at the right moment, ensuring that the division process proceeds smoothly.

Beyond revising a long-standing belief on cell division, this discovery also has important implications for research on genetic diseases. This is  particularly significant because errors in chromosome attachment and segregation, which could lead to an abnormal chromosome count, have been linked to the formation of cancer cells. Through the clarification of CENP-E’s role in the regulation of early chromosome attachment, scientists have also uncovered a potentially significant point in the process of division, giving us a better understanding of how such errors arise and how they can be prevented.