ASSOCIATION OF SPINDLE ASSEMBLY CHECKPOINT COMPONENT XMAD2 WITH UNATTACHED KINETOCHORES

The spindle assembly checkpoint delays anaphase until all chromosomes are attached to a mitotic spindle. The mad (mitotic arrest-deficient) and bub (budding uninhibited by benzimidazole) mutants of budding yeas t rack this checkpoint and fail to arrest the cell cycle when microtub ules are depolymerized. A frog homolog of MAD2 (XMAD2) was isolated an d found to play an essential role in the spindle assembly checkpoint i n frog egg extracts. XMAD2 protein associated with unattached kinetoch ores in prometaphase and in nocodazole-treated cells and disappeared f rom kinetochores at metaphase in untreated cells, suggesting that XMAD 2 plays a role in the activation of the checkpoint by unattached kinet ochores. This study furthers understanding of the mechanism of cell cy cle checkpoints in metazoa and provides a marker for studying the role of the spindle assembly checkpoint in the genetic instability of tumo rs.