Separating the spindle, checkpoint, and timer functions of BubR1.
BubR1 performs several roles during mitosis, affecting the spindle assembly checkpoint (SAC), mitotic timing, and spindle function, but the interdependence of these functions is unclear. We have analyzed in Drosophila melanogaster the mitotic phenotypes of kinase-dead (KD) BubR1 and BubR1 lacking the N-terminal KEN box. bubR1-KD individuals have a robust SAC but abnormal spindles with thin kinetochore fibers, suggesting that the kinase activity modulates microtubule capture and/or dynamics but is relatively dispensable for SAC function. In contrast, bubR1-KEN flies have normal spindles but no SAC. Nevertheless, mitotic timing is normal as long as Mad2 is present. Thus, the SAC, timer, and spindle functions of BubR1 are substantially separable. Timing is shorter in bubR1-KEN mad2 double mutants, yet in these flies, lacking both critical SAC components, chromosomes still segregate accurately, reconfirming that in Drosophila, reliable mitosis does not need the SAC.
Rahmani
Zohra
Z
Institut Jacques Monod, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7592, Université Paris Diderot, 75013 Paris, France.
Gagou
Mary E
ME
Lefebvre
Christophe
C
Emre
Doruk
D
Karess
Roger E
RE
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure
C506005:BubR1 protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins