@article {572816,
	title = {A small-molecule inhibitor of Mps1 blocks the spindle-checkpoint response to a lack of tension on mitotic chromosomes.},
	journal = {Curr Biol},
	volume = {15},
	number = {11},
	year = {2005},
	month = {2005 Jun 7},
	pages = {1070-6},
	abstract = {The spindle checkpoint prevents chromosome loss by preventing chromosome segregation in cells with improperly attached chromosomes [1, 2 and 3]. The checkpoint senses defects in the attachment of chromosomes to the mitotic spindle [4] and the tension exerted on chromosomes by spindle forces in mitosis [5, 6 and 7]. Because many cancers have defects in chromosome segregation, this checkpoint may be required for survival of tumor cells and may be a target for chemotherapy. We performed a phenotype-based chemical-genetic screen in budding yeast and identified an inhibitor of the spindle checkpoint, called cincreasin. We used a genome-wide collection of yeast gene-deletion strains and traditional genetic and biochemical analysis to show that the target of cincreasin is Mps1, a protein kinase required for checkpoint function [8]. Despite the requirement for Mps1 for sensing both the lack of microtubule attachment and tension at kinetochores, we find concentrations of cincreasin that selectively inhibit the tension-sensitive branch of the spindle checkpoint. At these concentrations, cincreasin causes lethal chromosome missegregation in mutants that display chromosomal instability. Our results demonstrate that Mps1 can be exploited as a target and that inhibiting the tension-sensitive branch of the spindle checkpoint may be a way of selectively killing cancer cells that display chromosomal instability.},
	keywords = {Bromobenzenes, Chromosome Segregation, Dimethyl Sulfoxide, DNA Primers, Dose-Response Relationship, Drug, Kinetochores, Microarray Analysis, Microtubules, Mitosis, Phenotype, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Spindle Apparatus},
	issn = {0960-9822},
	doi = {10.1016/j.cub.2005.05.020},
	author = {Dorer, Russell K and Zhong, Sheng and Tallarico, John A and Wong, Wing Hung and Mitchison, Timothy J. and Murray, Andrew W}
}
