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

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

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  • 1Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111, USA. Jennifer.Rhodes@fccc.edu

Abstract

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.

PMID:
19704007
[PubMed - indexed for MEDLINE]
PMCID:
PMC2772726
Free PMC Article
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