Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis.
Sister chromatids in mammalian cells remain attached mostly at their centromeres at metaphase because of the loss of cohesion along chromosome arms in prophase. Here, we report that Bub1 retains centromeric cohesion in mitosis of human cells. Depletion of Bub1 or Shugoshin (Sgo1) in HeLa cells by RNA interference causes massive missegregation of sister chromatids that originates at centromeres. Surprisingly, loss of chromatid cohesion in Bub1 and Sgo1 RNA-interference cells does not appear to require the full activation of separase but, instead, triggers a mitotic arrest that depends on Mad2 and Aurora B. Bub1 maintains the steady-state levels and centromeric localization of Sgo1. Therefore, Bub1 protects centromeric cohesion through Shugoshin in mitosis.
Tang
Zhanyun
Z
Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9041, USA.
Sun
Yuxiao
Y
Harley
Sara E
SE
Zou
Hui
H
Yu
Hongtao
H
D064107:Aurora Kinase B; D064127:Aurora Kinases; D002135:Calcium-Binding Proteins / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology*; D002503:Centromere / Q000648:ultrastructure*; D002842:Chromatids / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D064246:Mad2 Proteins; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009687:Nuclear Proteins / Q000502:physiology*; D011494:Protein Kinases / Q000737:chemistry / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D034622:RNA Interference; D012097:Repressor Proteins; D012854:Sister Chromatid Exchange; D008941:Spindle Apparatus
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C496644:SGO1 protein, human; D011494:Protein Kinases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases