Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling

• DOI: 10.1038/ncomms15822
• Publication Date: 2017-06-12T10:01:52Z
• Authors: Gang Zhang; Thomas Kruse; Blanca López-Méndez; Kathrine Beck Syl...; Dimitriya H. Garv...; Simone Schopper; Michael Lund Nielsen; Jakob Nilsson
• Keywords: BUB1; Spindle checkpoint; Mad2

Abstract Proper segregation of chromosomes depends on a functional spindle assembly checkpoint (SAC) and requires kinetochore localization the Bub1 Mad1/Mad2 proteins. Several aspects recruitment in human cells are unclear particular underlying direct interactions. Here we show that conserved domain 1 (CD1) binds directly to Mad1 phosphorylation site exists CD1 stimulates binding SAC signalling. Importantly, fusion minimal kinetochore-targeting fragments bypasses need for CD1, revealing main function is position close KNL1 MELT repeats. Furthermore, identify residues critical functionality, but not binding, arguing role checkpoint. This work dissects functionally relevant molecular interactions required signalling at kinetochores cells.