• Media type: E-Article
  • Title: A Bub1–Mad1 interaction targets the Mad1–Mad2 complex to unattached kinetochores to initiate the spindle checkpoint
  • Contributor: Moyle, Mark W.; Kim, Taekyung; Hattersley, Neil; Espeut, Julien; Cheerambathur, Dhanya K.; Oegema, Karen; Desai, Arshad
  • imprint: Rockefeller University Press, 2014
  • Published in: Journal of Cell Biology
  • Language: English
  • DOI: 10.1083/jcb.201311015
  • ISSN: 1540-8140; 0021-9525
  • Origination:
  • Footnote:
  • Description: <jats:p>Recruitment of Mad1–Mad2 complexes to unattached kinetochores is a central event in spindle checkpoint signaling. Despite its importance, the mechanism that recruits Mad1–Mad2 to kinetochores is unclear. In this paper, we show that MAD-1 interacts with BUB-1 in Caenorhabditis elegans. Mutagenesis identified specific residues in a segment of the MAD-1 coiled coil that mediate the BUB-1 interaction. In addition to unattached kinetochores, MAD-1 localized between separating meiotic chromosomes and to the nuclear periphery. Mutations in the MAD-1 coiled coil that selectively disrupt interaction with BUB-1 eliminated MAD-1 localization to unattached kinetochores and between meiotic chromosomes, both of which require BUB-1, and abrogated checkpoint signaling. The identified MAD-1 coiled-coil segment interacted with a C-terminal region of BUB-1 that contains its kinase domain, and mutations in this region prevented MAD-1 kinetochore targeting independently of kinase activity. These results delineate an interaction between BUB-1 and MAD-1 that targets MAD-1–MAD-2 complexes to kinetochores and is essential for spindle checkpoint signaling.</jats:p>
  • Access State: Open Access