During cell division, protein cables called microtubules latch on to a copy of every chromosome at a structure called the kinetochore and pull one of each to opposite poles of the dividing cell. In healthy cells, this choreographed segregation of chromosomes is monitored by a “spindle checkpoint” that halts cell division if even one kinetochore is not firmly attached to a microtubule, ensuring that chromosomes are equally distributed to each daughter cell. In a January paper in Science, Ludwig San Diego’s Arshad Desai, Pablo Lara-Gonzalez and colleagues detailed the mechanism by which the checkpoint is generated by the association of two proteins, Cdc20 and Mad2. Using a visual probe that tracks one of the proteins, the team detailed how Cdc20 and Mad2 are geometrically constrained at the kinetochore, held in a particular position by phosphorylation events that prime their interaction, and how their enzymatic substrates are locally delivered to them to generate the wait signal. The findings help explain why that signal is generated at kinetochores and not elsewhere in the cell, thereby ensuring that no chromosome is left behind.
This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).