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Abstract:
Almost two decades after their identification, the components of the
mitotic checkpoint are finally revealing their structural secrets. The
activation of Mad2, a central piece of the checkpoint protein machinery,
is linked to the rare ability of this protein to adopt two distinct
topologies. Current models of checkpoint function propose that the
topological transition between the two states of Mad2 is rate limiting
for checkpoint activation and is accelerated through a self-activation
process based on the direct interaction of the two Mad2 conformers.
These models add a molecular framework to an old theory that depicts
kinetochores as catalysts in the generation of the mitotic checkpoint
signal.
