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A mutation in separase causes genome instability and increased susceptibility to epithelial cancer.

Genes & development | Jan 1, 2007

Proper chromosome segregation is essential for maintenance of genomic integrity and instability resulting from failure of this process may contribute to cancer. Here, we demonstrate that a mutation in the mitotic regulator separase is responsible for the cell cycle defects seen in the zebrafish mutant, cease&desist (cds). Analysis of cds homozygous mutant embryos reveals high levels of polyploidy and aneuploidy, spindle defects, and a mitotic exit delay. Carcinogenesis studies demonstrated that cds heterozygous adults have a shift in tumor spectrum with an eightfold increase in the percentage of fish bearing epithelial tumors, indicating that separase is a tumor suppressor gene in vertebrates. These data strongly support a conserved cross-species role for mitotic checkpoint genes in genetic stability and epithelial carcinogenesis.

Pubmed ID: 17210788 RIS Download

Mesh terms: Animals | Bromodeoxyuridine | Carcinoma, Pancreatic Ductal | Cell Cycle | Cell Cycle Proteins | Disease Susceptibility | Embryo, Nonmammalian | Endopeptidases | Genomic Instability | Heterozygote | Homozygote | Intestinal Neoplasms | Mitosis | Mutation | Neoplasms, Glandular and Epithelial | Ploidies | Separase | Spindle Apparatus | Zebrafish