ZFIN ID: ZDB-PUB-090828-20
Emi1 Maintains Genomic Integrity during Zebrafish Embryogenesis and Cooperates with p53 in Tumor Suppression
Rhodes, J., Amsterdam, A., Sanda, T., Moreau, L.A., McKenna, K., Heinrichs, S., Ganem, N.J., Ho, K.W., Neuberg, D.S., Johnston, A., Ahn, Y., Kutok, J.L., Hromas, R., Wray, J., Lee, C., Murphy, C., Radke, I., Downing, J.R., Fleming, M.D., Macconaill, L.E., Amatruda, J.F., Gutierrez, A., Galinsky, I., Stone, R.M., Ross, E.A., Pellman, D.S., Kanki, J.P., and Look, A.T.
Date: 2009
Source: Molecular and cellular biology   29(21): 5911-5922 (Journal)
Registered Authors: Amatruda, James F., Amsterdam, Adam, Gutierrez, Alejandro, Kanki, John, Lee, Charles, Look, A. Thomas, Rhodes, Jennifer
Keywords: none
MeSH Terms:
  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Cycle Proteins/metabolism*
  • Cell Size
  • DNA Damage
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/pathology
  • Embryonic Development/genetics*
  • Genome/genetics*
  • Hematopoiesis
  • Mutation/genetics
  • Myeloid Cells/pathology
  • Neoplasms/pathology*
  • Phenotype
  • Tumor Suppressor Protein p53/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/metabolism*
PubMed: 19704007 Full text @ Mol. Cell. Biol.
A growing body of evidence indicates that early mitotic inhibitor 1 (Emi1) is essential for genomic stability, but how this function relates to embryonic development and cancer pathogenesis remains unclear. We have identified a zebrafish mutant line in which deficient emi1 gene expression results in multilineage hematopoietic defects and widespread developmental defects that are p53-independent. Cell cycle analyses of Emi1-depleted zebrafish or human cells showed chromosomal rereplication, and metaphase preparations from mutant zebrafish embryos revealed rereplicated, unsegregated chromosomes and polyploidy. Furthermore, EMI1-depleted mammalian cells were reliant on Topoisomerase IIalpha-dependent mitotic decatenation to progress through metaphase. Interestingly, the loss of a single emi1 allele in the absence of p53 enhanced the susceptibility of adult fish to neural sheath tumorigenesis. Our results cast Emi1 as a critical regulator of genomic fidelity during embryogenesis and suggest that this factor may act as a tumor suppressor.