Emi1 Maintains Genomic Integrity during Zebrafish Embryogenesis and Cooperates with p53 in Tumor Suppression
Year: 2009
Type: article
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.
Source: Molecular and Cellular Biology
DOI: 10.1128/mcb.00558-09
Authors: 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. MacConaill, James F. Amatruda, Alejandro Gutierrez, Ilene Galinsky, Richard M. Stone, Eric A. Ross, David S. Pellman, John P. Kanki, A. Thomas Look
Institutions: Fox Chase Cancer Center, Massachusetts Institute of Technology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard University, UNM Comprehensive Cancer Center, St. Jude Children's Research Hospital, Boston Children's Hospital, The University of Texas Southwestern Medical Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2050631304