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Cell division is one of the most thoroughly studied processes in biology, yet many of its details remain mysterious. A century-old puzzle surrounding the "crown" of cell division—the kinetochore corona—has now been solved by Verena Cmentowski and Andrea Musacchio at the Max Planck Institute of Molecular Â鶹ÒùÔºiology in Dortmund (MPI).

Their research, now in Science Advances, shows that the corona assembles through two parallel routes, beginning with a small protein "seed" and expanding into a multifunctional complex that ensures accurate chromosome segregation—and with it, the faithful transmission of life from one generation to the next.

A 20 year journey

Proteins are the workhorses of the cell, but many only function as part of larger multi-protein machines. These complexes perform essential tasks, such as muscle contraction, energy production, and gene regulation. One of the largest and most intricate of these machines is the kinetochore—the central hub of the cell division machinery.

The kinetochore connects chromosomes to spindle microtubules, corrects attachment errors, and triggers the separation of sister chromatids. It is built from more than 100 proteins, grouped into around 30 sub-complexes. Its outermost layer is the structure known as the corona.

"Studying the kinetochore is a tremendous challenge," says Musacchio, Director at the MPI. "You cannot simply extract it from the cell and analyze it—its size, multilayered design, and integration with other cellular structures make it extremely difficult to study."

Over the past two decades, his team has progressively reassembled larger portions of the kinetochore in the lab, culminating in a near-complete reconstruction and 3D structural map—a milestone in the field. Only recently did they succeed in rebuilding the corona itself, identifying its core components and overall architecture. Yet how this "crown" is put together had remained elusive—until now.

The crown revealed

"The corona holds some of the kinetochore's most intriguing secrets," says Cmentowski, a former Ph.D. student in Musacchio's laboratory. "Its assembly and disassembly are crucial, because they ensure correct chromosome alignment and regulate the timing of segregation through checkpoint signaling."

Cmentowski's work shows that corona formation begins with just two proteins, BUB1 and BUBR1. Together, they act as a seed, initiating the chain of interactions that drive corona assembly. From this starting point, the structure expands along two independent but interconnected routes, creating a cooperative and robust architecture.

Early in mitosis, the corona helps guide chromosomes toward the spindle equator and ensure their proper arrangement. Later, once microtubules have attached to the chromosomes, the corona disassembles, providing the signal for chromosome separation. Both steps are essential for accurate chromosome distribution.

"A heavy burden lies on the crown—errors in this process can lead to severe developmental problems and disease," notes Musacchio. "The dual-pathway assembly mechanism we discovered provides robustness, making the corona resilient to fluctuations in timing and allowing it to stay bound to chromosomes for as long as needed."