Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13.

ABSTRACT: The maintenance of genome stability during mitosis is coordinated by the spindle assembly checkpoint (SAC) through its effector the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex (APC/C, also known as the cyclosome)^1,2. Unattached kinetochores control MCC assembly by catalysing a change in the topology of the β-sheet of MAD2 (an MCC subunit), thereby generating the active closed MAD2 (C-MAD2) conformer^3-5. Disassembly of free MCC, which is required for SAC inactivation and chromosome segregation, is an ATP-dependent process driven by the AAA+ ATPase TRIP13. In combination with p31^comet, an SAC antagonist⁶, TRIP13 remodels C-MAD2 into inactive open MAD2 (O-MAD2)^7-10. Here, we present a mechanism that ex

SUBMITTER: Alfieri C 

PROVIDER: S-EPMC6057611 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature