• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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

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


  • Shepard JL
  • Amatruda JF
  • Finkelstein D
  • Ziai J
  • Finley KR
  • Stern HM
  • Chiang K
  • Hersey C
  • Barut B
  • Freeman JL
  • Lee C
  • Glickman JN
  • Kutok JL
  • Aster JC
  • Zon LI


Genes & development

Publication Data

January 1, 2007

Associated Grants

  • Agency: NHLBI NIH HHS, Id: T32 HL007627

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