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Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK

Correspondence to Stephen Taylor: stephen.taylor{at}manchester.ac.uk

Mps1 is an upstream component of the spindle assembly checkpoint, which, in human cells, is required for checkpoint activation in response to spindle damage but not apparently during an unperturbed mitosis. Mps1 also recruits Mad1 and Mad2 to kinetochores. However, whether the enzymatic activity of Mps1 is required for these processes is unclear. To address this question, we established an RNA interference (RNAi) complementation assay. Repression of Mps1 triggers premature anaphase, often with unaligned or maloriented chromosomes. This phenotype is rescued by an RNAi-resistant wild-type Mps1 transgene but not by a catalytically inactive mutant. An analogue-sensitive allele, Mps1^M602A, also rescues the RNAi-induced defect, but not when inhibited by the adenosine triphosphate analogue 1-NM-PP1. Thus, Mps1 activity does restrain anaphase during an unperturbed mitosis. Furthermore, although catalytically inactive Mps1 can restore kinetochore localization of Mad1, only the active kinase restores Mad2 localization. Thus, in human cells, Mps1 catalytic activity is required for spindle checkpoint function and recruitment of Mad2.

O. Staples' present address is Dept. of Surgery and Molecular Oncology, Ninewells Hospital, University of Dundee, Dundee DD1 9SY, Scotland, UK.

Abbreviations used in this paper: ACA, anticentromere antibody; APC/C, anaphase-promoting complex; Cenp, centromere protein; NEB, nuclear envelope breakdown; SAC, spindle assembly checkpoint; shRNA, short hairpin RNA.

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