First published online March 12, 2004
Journal of Cell Science 117, 802e (2004)
© The Company of Biologists Limited
Assembling the spindle checkpoint
The spindle assembly checkpoint ensures that daughter cells each inherit the correct number of chromosomes at mitosis, delaying sister chromatid separation until chromosomes are correctly aligned. Checkpoint proteins such as Bub1, BubR1 and Mad2 are assembled at kinetochores - the complexes that link centromeres to spindle microtubules. Whether their order of arrival is important is unclear, however, given conflicting studies in Xenopus and mammals. Stephen Taylor and co-workers have therefore combined quantitative immunofluorescence microscopy with RNAi directed against various human checkpoint proteins to dissect the kinetochore assembly process (see p. 1577). They find that Bub1, which arrives first, is essential for subsequent recruitment of BubR1, the motor protein CENP-E and Mad2 - unlike in Xenopus, Bub1 recruitment does not require BubR1. In addition, the authors demonstrate that arrival of Mad2 depends on CENP-E, whose recruitment in turn requires BubR1. Intriguingly, Taylor and co-workers also observe that RNAi directed against Bub1 does not affect the checkpoint's activity. One possibility is obviously that a parallel checkpoint pathway exists and compensates in the absence of Bub1; alternatively, the small amount of Bub1 remaining after RNAi might still be sufficient for effective checkpoint signalling.
Related articles in JCS:
- Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression
- Victoria L. Johnson, Maria I. F. Scott, Sarah V. Holt, Deema Hussein, and Stephen S. Taylor
JCS 2004 117: 1577-1589.
[Abstract]
[Full Text]
