Unknown

Dataset Information

0

TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response.


ABSTRACT: The spindle checkpoint acts during cell division to prevent aneuploidy, a hallmark of cancer. During checkpoint activation, Mad1 recruits Mad2 to kinetochores to generate a signal that delays anaphase onset. Yet, whether additional factors contribute to Mad2's kinetochore localization remains unclear. Here, we report that the conserved AAA+ ATPase TRIP13(PCH-2) localizes to unattached kinetochores and is required for spindle checkpoint activation in Caenorhabditis elegans. pch-2 mutants effectively localized Mad1 to unattached kinetochores, but Mad2 recruitment was significantly reduced. Furthermore, we show that the C. elegans orthologue of the Mad2 inhibitor p31(comet)(CMT-1) interacts with TRIP13(PCH-2) and is required for its localization to unattached kinetochores. These factors also genetically interact, as loss of p31(comet)(CMT-1) partially suppressed the requirement for TRIP13(PCH-2) in Mad2 localization and spindle checkpoint signaling. These data support a model in which the ability of TRIP13(PCH-2) to disassemble a p31(comet)/Mad2 complex, which has been well characterized in the context of checkpoint silencing, is also critical for spindle checkpoint activation.

SUBMITTER: Nelson CR 

PROVIDER: S-EPMC4639874 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

altmetric image

Publications

TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response.

Nelson Christian R CR   Hwang Tom T   Chen Pin-Hsi PH   Bhalla Needhi N  

The Journal of cell biology 20151102 3


The spindle checkpoint acts during cell division to prevent aneuploidy, a hallmark of cancer. During checkpoint activation, Mad1 recruits Mad2 to kinetochores to generate a signal that delays anaphase onset. Yet, whether additional factors contribute to Mad2's kinetochore localization remains unclear. Here, we report that the conserved AAA+ ATPase TRIP13(PCH-2) localizes to unattached kinetochores and is required for spindle checkpoint activation in Caenorhabditis elegans. pch-2 mutants effectiv  ...[more]

Similar Datasets

| S-EPMC2080909 | biostudies-literature
| S-EPMC3989695 | biostudies-literature
| S-EPMC3941058 | biostudies-literature
| S-EPMC2526710 | biostudies-literature
| S-EPMC6446853 | biostudies-literature
| S-EPMC2150717 | biostudies-literature
| S-EPMC8406419 | biostudies-literature
| S-EPMC2132829 | biostudies-literature
| S-EPMC6485516 | biostudies-literature
| S-EPMC2993392 | biostudies-literature