{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:41:51Z","timestamp":1768484511574,"version":"3.49.0"},"posted":{"date-parts":[[2019,6,4]]},"group-title":"Cell Biology","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2019,6,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The strength of the Spindle Assembly Checkpoint (SAC) depends on the amount of the Mad1-C-Mad2 heterotetramer at kinetochores but also on its binding to Megator\/Tpr at nuclear pore complexes (NPCs) during interphase. However, the molecular underpinnings controlling the spatiotemporal redistribution of Mad1-C-Mad2 as cells progress into mitosis remain elusive. Here, we show that Mps1-mediated phosphorylation of Megator\/Tpr abolishes its interaction with Mad1\n                  <jats:italic>in vitro<\/jats:italic>\n                  and in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  cells. Timely activation of Mps1 during prophase triggers Mad1 release from NPCs, which we find to be required for competent kinetochore recruitment of Mad1-C-Mad2 and robust checkpoint response. Importantly, preventing Mad1 binding to Megator\/Tpr rescues the fidelity of chromosome segregation and aneuploidy in larval neuroblasts of\n                  <jats:italic>Drosophila mps1<\/jats:italic>\n                  -null mutants. Our findings demonstrate that the subcellular localization of Mad1 is stringently coordinated with cell cycle progression by kinetochore-extrinsic activity of Mps1. This ensures that both NPCs in interphase and kinetochores in mitosis can generate anaphase inhibitors to efficiently preserve genomic stability.\n                <\/jats:p>","DOI":"10.1101\/659938","type":"posted-content","created":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T15:45:17Z","timestamp":1559663117000},"source":"Crossref","is-referenced-by-count":0,"title":["Mps1 releases Mad1 from nuclear pores to ensure a robust mitotic checkpoint and accurate chromosome segregation"],"prefix":"10.64898","author":[{"given":"Mariana","family":"Osswald","sequence":"first","affiliation":[]},{"given":"Sofia","family":"Cunha-Silva","sequence":"additional","affiliation":[]},{"given":"Jana","family":"Goemann","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Barbosa","sequence":"additional","affiliation":[]},{"given":"Luis M","family":"Santos","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7365-904X","authenticated-orcid":false,"given":"Pedro","family":"Resende","sequence":"additional","affiliation":[]},{"given":"Tanja","family":"Bange","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2963-9380","authenticated-orcid":false,"given":"Claudio 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