title: Arrayed BUB recruitment modules in the kinetochore scaffold KNL1 promote accurate chromosome segregation.
abstract: Fidelity of chromosome segregation relies on coordination of chromosome biorientation and the spindle checkpoint. Central to this is the kinetochore scaffold KNL1 that integrates the functions of various mitotic regulators including BUB1 and BUBR1. We show that KNL1 contains an extensive array of short linear sequence modules that encompass TxxΩ and MELT motifs and that can independently localize BUB1. Engineered KNL1 variants with few modules recruit low levels of BUB1 to kinetochores but support a robust checkpoint. Increasing numbers of modules concomitantly increase kinetochore BUB1 levels and progressively enhance efficiency of chromosome biorientation. Remarkably, normal KNL1 function is maintained by replacing all modules with a short array of naturally occurring or identical, artificially designed ones. A minimal array of generic BUB recruitment modules in KNL1 thus suffices for accurate chromosome segregation. Widespread divergence in the amount and sequence of these modules in KNL1 homologues may represent flexibility in adapting regulation of mitotic processes to altered requirements for chromosome segregation during evolution.
authors.forename: Mathijs
authors.initials: M
authors.lastname: Vleugel
authors.forename: Eelco
authors.initials: E
authors.lastname: Tromer
authors.forename: Manja
authors.initials: M
authors.lastname: Omerzu
authors.forename: Vincent
authors.initials: V
authors.lastname: Groenewold
authors.forename: Wilco
authors.initials: W
authors.lastname: Nijenhuis
authors.forename: Berend
authors.initials: B
authors.lastname: Snel
authors.forename: Geert J P L
authors.initials: GJ
authors.lastname: Kops
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D059447:Cell Cycle Checkpoints; D020090:Chromosome Segregation / Q000502:physiology*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016415:Sequence Alignment
chemical_list: C472643:Knl1 protein, human; D008869:Microtubule-Associated Proteins; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases