title: Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression.
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.
authors.affiliation: Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111, USA. Jennifer.Rhodes@fccc.edu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rhodes
authors.forename: Adam
authors.initials: A
authors.lastname: Amsterdam
authors.forename: Takaomi
authors.initials: T
authors.lastname: Sanda
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Moreau
authors.forename: Keith
authors.initials: K
authors.lastname: McKenna
authors.forename: Stefan
authors.initials: S
authors.lastname: Heinrichs
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Ganem
authors.forename: Karen W
authors.initials: KW
authors.lastname: Ho
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: Adam
authors.initials: A
authors.lastname: Johnston
authors.forename: Yebin
authors.initials: Y
authors.lastname: Ahn
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Robert
authors.initials: R
authors.lastname: Hromas
authors.forename: Justin
authors.initials: J
authors.lastname: Wray
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Carly
authors.initials: C
authors.lastname: Murphy
authors.forename: Ina
authors.initials: I
authors.lastname: Radtke
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
authors.forename: Laura E
authors.initials: LE
authors.lastname: MacConaill
authors.forename: James F
authors.initials: JF
authors.lastname: Amatruda
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Ilene
authors.initials: I
authors.lastname: Galinsky
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Eric A
authors.initials: EA
authors.lastname: Ross
authors.forename: David S
authors.initials: DS
authors.lastname: Pellman
authors.forename: John P
authors.initials: JP
authors.lastname: Kanki
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D048429:Cell Size; D004249:DNA Damage; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics*; D016678:Genome / Q000235:genetics*; D006410:Hematopoiesis; D009154:Mutation / Q000235:genetics; D022423:Myeloid Cells / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*; D010641:Phenotype; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C530717:fbxo5 protein, zebrafish
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