PCH-2TRIP13 regulates spindle checkpoint strength

Spindle checkpoint strength, defined as the length of the cell cycle delay imposed by the spindle checkpoint, is dictated by three criteria: the number of unattached kinetochores, cell volume and cell fate. However, how checkpoint strength is regulated is unknown. We show that the conserved AAA-ATPase, PCH-2, which remodels the essential checkpoint effector Mad2 from an active conformation to an inactive one, controls checkpoint strength in C. elegans. When we genetically manipulate embryos to decrease cell volume, PCH-2 is no longer required for the spindle checkpoint or recruitment of Mad2 at unattached kinetochores, showing that PCH-2 is essential for a robust checkpoint in large cells. This role in checkpoint strength is not limited to large cells: germline precursor cells exhibit a stronger checkpoint than their somatic counterparts and this also relies on PCH-2. PCH-2 is more highly enriched in germline precursor cells than in somatic cells and this enrichment relies on a conserved factor that induces asymmetry in the early embryo. Finally, the stronger checkpoint in germline precursor cells also depends on CMT-1, which is essential for both PCH-2u0027s localization to unattached kinetochores and its enrichment in germline precursor cells. Thus, PCH-2u0027s ability to regulate the availability of an inactive but necessary checkpoint precursor at or near unattached kinetochores governs checkpoint strength.