The spindle checkpoint: structural insights into dynamic signalling

Authors:
Publisher website
Google Scholar
Abstract
The spindle checkpoint monitors the interactions between chromosomes and microtubules. The Mad and Bub proteins are core components of this cell-cycle control. The checkpoint can monitor kinetochore–microtubule attachment and/or the tension exerted at kinetochores upon bipolar attachment. Kinetochores are a key site for monitoring defects and signalling, and for effecting the cell-cycle delay. They can act as the catalytic site for the production of the checkpoint signal ('wait anaphase'), which must then be transmitted globally. Microtubule motors (CENP-E and dynein) and protein kinases (Aurora B) have roles in kinetochore binding and bipolar attachment, and could be involved in sensing tension. Mad2 and other checkpoint proteins have a very dynamic association with kinetochores (half-life of ∼20 s). These dynamics might also be involved in checkpoint silencing. Several checkpoint components (Mad2, BubR1, CENP-E and Rod) are continuously removed from kinetochores by a dynein-dependent mechanism. Two related interactions of Mad2 (with Mad1 and Cdc20) are central to the checkpoint, and crystal structures of a Mad1–Mad2 complex have revealed a 'safety-belt' bind-and-release mechanism. Mad2 and/or BubR1 complexes might stoichiometrically inhibit Cdc20 and thereby the activity of the anaphase-promoting complex.

This publication has 126 references indexed in Scilit: