Watching TRIP13 at work

When a cell gets ready to divide, it needs to make sure all of its chromosomes are lined up and ready to go, so none of them gets left behind. The Spindle Assembly Checkpoint monitors this process, and two key elements of the checkpoint pathway are the proteins MAD2 and TRIP13. In a new paper just published in The EMBO Journal, we reveal the molecular mechanism of a key step in this checkpoint pathway: its inactivation. We show that TRIP13 binds and pulls on MAD2's N-terminus to unfold the protein and disassemble the MAD2-containing mitotic checkpoint complex. Collaborating with Attila Toth in Dresden, we show that TRIP13 acts on the MAD2-related meiotic HORMADs using the same mechanism. Also contributing to the project were the labs of Don Cleveland here at Ludwig San Diego, and Franz Herzog in Munich. Great work everyone!