Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression

Mol Cell Biol. 2009 Nov;29(21):5911-22. doi: 10.1128/MCB.00558-09. Epub 2009 Aug 24.


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 relied on topoisomerase II alpha-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 the factor may act as a tumor suppressor.

Publication types

  • Research Support, N.I.H., Extramural

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*


  • Cell Cycle Proteins
  • Tumor Suppressor Protein p53
  • Zebrafish Proteins
  • fbxo5 protein, zebrafish