TY - JOUR T1 - PCH-2<sup>TRIP13</sup> regulates spindle checkpoint strength JF - bioRxiv DO - 10.1101/389080 SP - 389080 AU - Lénaïg Défachelles AU - Anna E. Russo AU - Christian R. Nelson AU - Needhi Bhalla Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/04/389080.abstract N2 - Spindle checkpoint strength is dictated by the number of unattached kinetochores, cell volume and cell fate. We show that the conserved AAA-ATPase, PCH-2/TRIP13, which remodels the checkpoint effector Mad2 from an active conformation to an inactive one, controls checkpoint strength in C. elegans. When we manipulate embryos to decrease cell volume, PCH-2 is no longer required for the spindle checkpoint or recruitment of Mad2 at unattached kinetochores. This role is not limited to large cells: the stronger checkpoint in germline precursor cells also depends on PCH-2. PCH-2 is enriched in germline precursor cells and this enrichment relies on a conserved factor that induces asymmetry in the early embryo. Finally, the stronger checkpoint in germline precursor cells is regulated by CMT-1, the ortholog of p31comet, which is required for both PCH-2’s localization to unattached kinetochores and its enrichment in germline precursor cells. Thus, PCH-2, likely by regulating the availability of inactive Mad2 at and near unattached kinetochores, governs checkpoint strength. ER -