TRIP13 Functions in the Establishment of the Spindle Assembly Checkpoint by Replenishing O-MAD2.

Abstract:

:The spindle assembly checkpoint (SAC) prevents premature segregation of chromosomes during mitosis. This process requires structural remodeling of MAD2 from O-MAD2 to C-MAD2 conformation. After the checkpoint is satisfied, C-MAD2 is reverted to O-MAD2 to allow anaphase-promoting complex/cyclosome (APC/C) to trigger anaphase. Recently, the AAA+-ATPase TRIP13 was shown to act in concert with p31comet to catalyze C- to O-MAD2. Paradoxically, although C-MAD2 is present in TRIP13-deficient cells, the SAC cannot be activated. Using a degron-mediated system to uncouple TRIP13 from O- and C-MAD2 equilibrium, we demonstrated that the loss of TRIP13 did not immediately abolish the SAC, but the resulting C-MAD2-only environment was insufficient to enable the SAC. These results favor a model in which MAD2-CDC20 interaction is coupled directly to the conversion of O- to C-MAD2 instead of one that involves unliganded C-MAD2. TRIP13 replenishes the O-MAD2 pool for activation by unattached kinetochores.

journal_name

Cell Rep

journal_title

Cell reports

authors

Ma HT,Poon RYC

doi

10.1016/j.celrep.2018.01.027

subject

Has Abstract

pub_date

2018-02-06 00:00:00

pages

1439-1450

issue

6

issn

2211-1247

pii

S2211-1247(18)30059-7

journal_volume

22

pub_type

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