PUBLICATION
A mutation in separase causes genome instability and increased susceptibility to epithelial cancer
- Authors
- Shepard, J.L., Amatruda, J.F., Finkelstein, D., Ziai, J., Finley, K.R., Stern, H.M., Chiang, K., Hersey, C., Barut, B., Freeman, J.L., Lee, C., Glickman, J.N., Kutok, J.L., Aster, J.C., and Zon, L.I.
- ID
- ZDB-PUB-070122-27
- Date
- 2007
- Source
- Genes & Development 21(1): 55-59 (Journal)
- Registered Authors
- Amatruda, James F., Barut, Bruce, Freeman, Jennifer, Hersey, Candace, Lee, Charles, Shepard, Jennifer, Stern, Howard, Ziai, James, Zon, Leonard I.
- Keywords
- Cancer, chromosome segregation, mitotic checkpoint, zebrafish
- MeSH Terms
-
- Cell Cycle Proteins/genetics*
- Genomic Instability*
- Mutation*
- Carcinoma, Pancreatic Ductal/etiology
- Carcinoma, Pancreatic Ductal/pathology
- Mitosis*
- Disease Susceptibility*
- Heterozygote
- Cell Cycle
- Intestinal Neoplasms/etiology
- Intestinal Neoplasms/pathology
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Bromodeoxyuridine
- Animals
- Ploidies
- Endopeptidases/genetics*
- Homozygote
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism
- Spindle Apparatus/genetics
- Spindle Apparatus/pathology
- Neoplasms, Glandular and Epithelial/etiology*
- Neoplasms, Glandular and Epithelial/pathology
- Separase
- PubMed
- 17210788 Full text @ Genes & Dev.
Citation
Shepard, J.L., Amatruda, J.F., Finkelstein, D., Ziai, J., Finley, K.R., Stern, H.M., Chiang, K., Hersey, C., Barut, B., Freeman, J.L., Lee, C., Glickman, J.N., Kutok, J.L., Aster, J.C., and Zon, L.I. (2007) A mutation in separase causes genome instability and increased susceptibility to epithelial cancer. Genes & Development. 21(1):55-59.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping