Bub1 was one of the first protein kinases identified as a component of the spindle-assembly checkpoint (SAC), but evidence that its kinase activity is essential for regulating the SAC in mammalian cells is conflicting. On page 653, David Perera and Stephen Taylor now shed light on this issue by carrying out complementation studies in Bub1-null mouse embryonic fibroblasts (MEFs), which exhibit a nonfunctional SAC, abnormal chromosome alignment and defective localisation of Sgo1 (which protects sister-chromatid cohesion at centromeres). They find that adenoviral-mediated expression of Bub1 lacking the kinase domain, or containing a point mutation in the kinase domain, restores SAC function and chromosome alignment in Bub1-null MEFs to the same extent as does wild-type Bub1. By contrast, neither mutant restores the defective localisation of Sgo1 at centromeres in prometaphase Bub1-null MEFs. But why does Sgo1 mislocalisation not cause defective centromeric cohesion in this context? The authors go on to show that the pattern of Sgo1 localisation has three distinct stages during the late cell cycle: it localises at centromeric heterochromatin in early to mid G2, is diffuse in late G2 and early prophase, and returns to centromeres at the onset of mitosis. The authors conclude that the kinase activity of Bub1 is only required for Sgo1 localisation in the latter phase, which is not essential for centromeric cohesion.
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