title: Kinetochore-localized BUB-1/BUB-3 complex promotes anaphase onset in C. elegans.
abstract: The conserved Bub1/Bub3 complex is recruited to the kinetochore region of mitotic chromosomes, where it initiates spindle checkpoint signaling and promotes chromosome alignment. Here we show that, in contrast to the expectation for a checkpoint pathway component, the BUB-1/BUB-3 complex promotes timely anaphase onset in Caenorhabditis elegans embryos. This activity of BUB-1/BUB-3 was independent of spindle checkpoint signaling but required kinetochore localization. BUB-1/BUB-3 inhibition equivalently delayed separase activation and other events occurring during mitotic exit. The anaphase promotion function required BUB-1's kinase domain, but not its kinase activity, and this function was independent of the role of BUB-1/BUB-3 in chromosome alignment. These results reveal an unexpected role for the BUB-1/BUB-3 complex in promoting anaphase onset that is distinct from its well-studied functions in checkpoint signaling and chromosome alignment, and suggest a new mechanism contributing to the coordination of the metaphase-to-anaphase transition.
authors.affiliation: Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037 Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037.
authors.forename: Taekyung
authors.initials: T
authors.lastname: Kim
authors.affiliation: Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037 Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Moyle
authors.affiliation: Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037 Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lara-Gonzalez
authors.affiliation: Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037 Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037.
authors.forename: Christian
authors.initials: C
authors.lastname: De Groot
authors.affiliation: Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037 Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037.
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
authors.affiliation: Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037 Ludwig Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037 abdesai@ucsd.edu.
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
mesh_terms: D000705:Anaphase; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D002875:Chromosomes / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C000599843:BUB-3 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; C588208:bub-1 protein, C elegans