Chk1 is required for spindle checkpoint function

Zachos, G., Black, E. J., Walker, M., Scott, M. T. , Vagnarelli, P., Earnshaw, W. C. and Gillespie, D. A.F. (2007) Chk1 is required for spindle checkpoint function. Developmental Cell, 12(2), pp. 247-260. (doi: 10.1016/j.devcel.2007.01.003) (PMID:17276342)

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The spindle checkpoint delays anaphase onset in cells with mitotic spindle defects. Here, we show that Chk1, a component of the DNA damage and replication checkpoints, protects vertebrate cells against spontaneous chromosome missegregation and is required to sustain anaphase delay when spindle function is disrupted by taxol, but not when microtubules are completely depolymerized by nocodazole. Spindle checkpoint failure in Chk1-deficient cells correlates with decreased Aurora-B kinase activity and impaired phosphorylation and kinetochore localization of BubR1. Furthermore, Chk1 phosphorylates Aurora-B and enhances its catalytic activity in vitro. We propose that Chk1 augments spindle checkpoint signaling and is required for optimal regulation of Aurora-B and BubR1 when kinetochores produce a weakened signal. In addition, Chk1-deficient cells exhibit increased resistance to taxol. These results suggest a mechanism through which Chk1 could protect against tumorigenesis through its role in spindle checkpoint signaling.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Walker, Mr Mark and Gillespie, Professor David and Scott, Dr Mary and Zachos, Dr George
Authors: Zachos, G., Black, E. J., Walker, M., Scott, M. T., Vagnarelli, P., Earnshaw, W. C., and Gillespie, D. A.F.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Developmental Cell

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