title: Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2.
abstract: Chromosome segregation during mitosis requires chromosomes to undergo bipolar attachment on spindle microtubules (MTs) and subsequent silencing of the spindle checkpoint. Here, we describe the identification and characterisation of a novel spindle and kinetochore (KT)-associated complex that is required for timely anaphase onset. The complex comprises at least two proteins, termed Ska1 (Spindle and KT Associated 1) and Ska2. Ska1 associates with KTs following MT attachment during prometaphase. Ska1 and Ska2 interact with each other and Ska1 is required for Ska2 stability in vivo. Depletion of either Ska1 or Ska2 by small interfering RNA results in the loss of both proteins from the KT. The absence of Ska proteins does not disrupt overall KT structure, but KT fibres show an increased cold-sensitivity. Most strikingly, Ska-depleted cells undergo a prolonged checkpoint-dependent delay in a metaphase-like state. This delay is characterised by the recruitment of Mad2 protein to a few KTs and the occasional loss of individual chromosomes from the metaphase plate. These data suggest that the Ska1/2 complex plays a critical role in the maintenance of the metaphase plate and/or spindle checkpoint silencing.
authors.affiliation: Department of Cell Biology, Max-Planck-Institute for Biochemistry, Martinsried, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Hanisch
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Silljé
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
mesh_terms: D000705:Anaphase / Q000187:drug effects / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D008941:Spindle Apparatus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D034741:RNA, Small Interfering; C516427:SKA1 protein, human; C516428:SKA2 protein, human