TOPP puts an end to the pause
Equal distribution of all chromosomes is an essential part of cell division. Up till then the division is paused. Chinese researchers now show in Scientific Advances that the TOPP proteins tell when this pause stops.
During cell division the cell makes sure that each of its daughter cells gets a complete set of chromosomes. To manage that, the cell connects each chromosome with microtubules to the so-called mitotic spindle.
A cell division manager, KLN1, controls if all chromosomes are connected. KNL1 has an army of regulators with him. As long as KLN1 sees that not all chromosomes are connected to the mitotic spindle, those regulators stop the division. The researchers decided to study which messengers tell KLN1 that all the chromosomes are connected.
Binding of TOPP to KLN1 resulted in that the division pausing regulators melt away
For this the researchers looked at the plant relatives of the animal KLN1 messengers: The TOPP proteins. These, it turned out, bind KLN1 when all the chromosomes are connected to the mitotic spindle. After binding of the TOPP proteins, cell division proceeded. Prevented the researchers the TOPP proteins from binding to KLN1, then cell division stayed on halt for a long time, although eventually the cell would still divide.
Subsequently the researchers analysed what happens with the army of regulators after TOPP binds to KLN1. For this the researchers looked at KLN1 variants that did or did not bind TOPP proteins. During this the researchers noticed that after binding of TOPP to KLN1 the army of regulators that stop the division melted away. But when TOPP was prevented from binding KLN1, then the regulators stayed with KLN1, regardless of the binding of the chromosomes to the mitotic spindle.
When the researchers zoomed out to a whole plant, they noticed that when TOPP proteins can’t do their job, it severely hinders the growth of the plant. With an early death as result. This indicates the importance of not only checking if all the requirements are met, but also of not dallying too long when they are.
Literature
Ying He et al., Arabidopsis KNL1 recruits type one protein phosphatase to kinetochores to silence the spindle assembly checkpoint. Sci. Adv. 11, eadq4033 (2025). DOI:10.1126/sciadv.adq4033
