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 RIS Download
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