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

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.

Pubmed ID: 19704007

Authors

  • Rhodes J
  • Amsterdam A
  • Sanda T
  • Moreau LA
  • McKenna K
  • Heinrichs S
  • Ganem NJ
  • Ho KW
  • Neuberg DS
  • Johnston A
  • Ahn Y
  • Kutok JL
  • Hromas R
  • Wray J
  • Lee C
  • Murphy C
  • Radtke I
  • Downing JR
  • Fleming MD
  • MacConaill LE
  • Amatruda JF
  • Gutierrez A
  • Galinsky I
  • Stone RM
  • Ross EA
  • Pellman DS
  • Kanki JP
  • Look AT

Journal

Molecular and cellular biology

Publication Data

November 13, 2009

Associated Grants

  • Agency: NIDDK NIH HHS, Id: K01 DK69672
  • Agency: NCI NIH HHS, Id: P01 CA66996-11A1
  • Agency: NCI NIH HHS, Id: R01 CA111560
  • Agency: NCI NIH HHS, Id: R01 CA93152
  • Agency: NCRR NIH HHS, Id: R01 RR12589

Mesh Terms

  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Size
  • DNA Damage
  • Embryo, Nonmammalian
  • Embryonic Development
  • Genome
  • Hematopoiesis
  • Mutation
  • Myeloid Cells
  • Neoplasms
  • Phenotype
  • Tumor Suppressor Protein p53
  • Zebrafish
  • Zebrafish Proteins