The faithful segregation of chromosomes into daughter cells is essential for cellular and organismal viability. Errors in this process cause aneuploidy, a hallmark of cancer and several congenital diseases. For proper separation, chromosomes attach to microtubules of the mitotic spindle via their kinetochores, large protein structures assembled on centromeric chromatin. Kinetochores are also crucial for a cell cycle feedback mechanism known as the spindle assembly checkpoint (SAC). The SAC forces cells to remain in mitosis until all chromosomes are properly attached to microtubules. At the beginning of mitosis, the SAC proteins - Mad1, Mad2, Bub1, Bub3, BubR1, Mps1, and Cdc20 - are recruited to kinetochores in a hierarchical and interdependent fashion (Fig A). There they monitor, in ways that are not fully clarified, the formation of kinetochore-microtubule attachments. Two studies recently published in EMBO reports by the groups of Silke Hauf and Jakob Nilsson, and a recent study by London and Biggins in Genes & Development, shed new light on the conserved SAC protein Mad1. Two recent studies in EMBO reports identify a new role for Mad1 in the spindle assembly checkpoint (SAC), which prevents cells from dividing until all chromosomes are attached to the spindle. These findings are integrated into an updated model of SAC activation.
ASJC Scopus subject areas
- Molecular Biology