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

Jennifer Rhodes, Adam Amsterdam, Takaomi Sanda, Lisa A. Moreau, Keith McKenna, Stefan Heinrichs, Neil J. Ganem, Karen W. Ho, Donna S. Neuberg, Adam Johnston, Yebin Ahn, Jeffery L. Kutok, Robert Hromas, Justin Wray, Charles Lee, Carly Murphy, Ina Radtke, James R. Downing, Mark D. Fleming, Laura E. MacConaillJames F. Amatruda, Alejandro Gutierrez, Ilene Galinsky, Richard M. Stone, Eric A. Ross, David S. Pellman, John P. Kanki, A. Thomas Look

Research output: Contribution to journalArticle

27 Scopus citations

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 IIα-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.

Original languageEnglish (US)
Pages (from-to)5911-5922
Number of pages12
JournalMolecular and cellular biology
Volume29
Issue number21
DOIs
StatePublished - Nov 1 2009

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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., Radtke, I., Downing, J. R., Fleming, M. D., ... Look, A. T. (2009). Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression. Molecular and cellular biology, 29(21), 5911-5922. https://doi.org/10.1128/MCB.00558-09