BUB-1 makes kinetochores MAD

Moyle et al. describe how the C. elegans BUB-1 kinase helps recruit the spindle checkpoint proteins MAD-1 and MAD-2 to unattached kinetochores.

During mitosis, the MAD-1–MAD-2 complex binds to kinetochores that haven’t attached to the spindle and generates a signal that prevents cells from entering anaphase until the correct attachments are formed. Several kinetochore proteins are required to localize MAD-1–MAD-2 to unattached kinetochores in vivo, but whether any of these proteins recruit the checkpoint complex directly is unknown.

Moyle et al. screened a library of kinetochore proteins and found that C. elegans MAD-1 interacted with BUB-1, a kinase required for MAD-1–MAD-2 localization. Mutations in MAD-1’s central coiled-coil domain disrupted the protein’s interaction with BUB-1 and inhibited the recruitment of MAD-1 and MAD-2 to unattached kinetochores in worms, thereby preventing them from activating the spindle checkpoint and delaying anaphase. MAD-1 interacted with BUB-1’s C-terminal kinase domain, and mutations in this domain blocked MAD-1’s recruitment to unattached kinetochores. But BUB-1’s kinase activity wasn’t required for MAD-1’s localization, suggesting that BUB-1 recruits MAD-1 to kinetochores directly.

Senior author Arshad Desai now wants to investigate how other kinetochore proteins, such as the microtubule-binding protein Ndc80, contribute to MAD-1–MAD-2 recruitment and ensure that the complex is removed once kinetochores are correctly attached to the mitotic spindle.