Emi1 Maintains Genomic Integrity during Zebrafish Embryogenesis and Cooperates with p53 in Tumor Suppression (cid:1)

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

[1]  James R. Downing,et al.  Genomic Analysis of the Clonal Origins of Relapsed Acute Lymphoblastic Leukemia , 2008, Science.

[2]  Amy E. Hawkins,et al.  DNA sequencing of a cytogenetically normal acute myeloid leukemia genome , 2008, Nature.

[3]  R. Hromas,et al.  The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation , 2008, Nucleic acids research.

[4]  S. Holley,et al.  Cell cycle progression is required for zebrafish somite morphogenesis but not segmentation clock function , 2008, Development.

[5]  D. Green,et al.  Chk1 Suppresses a Caspase-2 Apoptotic Response to DNA Damage that Bypasses p53, Bcl-2, and Caspase-3 , 2008, Cell.

[6]  T. Lister,et al.  Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease , 2008, Proceedings of the National Academy of Sciences.

[7]  N. Lehman,et al.  Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma , 2008, Modern Pathology.

[8]  N. A. Walton,et al.  Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis , 2007, Proceedings of the National Academy of Sciences.

[9]  N. Lehman,et al.  Loss of Emi1-Dependent Anaphase-Promoting Complex/Cyclosome Inhibition Deregulates E2F Target Expression and Elicits DNA Damage-Induced Senescence , 2007, Molecular and Cellular Biology.

[10]  Maitreya J. Dunham,et al.  Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast , 2007, Science.

[11]  L. Chin,et al.  Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers , 2007, Nature.

[12]  J. Pines,et al.  Emi1 is needed to couple DNA replication with mitosis but does not regulate activation of the mitotic APC/C , 2007, The Journal of cell biology.

[13]  R. Tibshirani,et al.  Oncogenic regulators and substrates of the anaphase promoting complex/cyclosome are frequently overexpressed in malignant tumors. , 2007, The American journal of pathology.

[14]  Anindya Dutta,et al.  The APC/C inhibitor, Emi1, is essential for prevention of rereplication. , 2007, Genes & development.

[15]  J. Freeman,et al.  A mutation in separase causes genome instability and increased susceptibility to epithelial cancer. , 2007, Genes & development.

[16]  N. Lehman,et al.  Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor. , 2006, Genes & development.

[17]  Y. Toyoda,et al.  Coordinated requirements of human topo II and cohesin for metaphase centromere alignment under Mad2-dependent spindle checkpoint surveillance. , 2006, Molecular biology of the cell.

[18]  D. Lim,et al.  Mouse emi1 Has an Essential Function in Mitotic Progression during Early Embryogenesis† , 2006 .

[19]  A. Teigler‐Schlegel,et al.  Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6;11)(q24.1;p15.5) resulting in a NUP98–C6orf80 fusion in a case of acute megakaryoblastic leukemia , 2005, Genes, chromosomes & cancer.

[20]  L. Zon,et al.  tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Look,et al.  Interplay of pu.1 and gata1 determines myelo-erythroid progenitor cell fate in zebrafish. , 2005, Developmental cell.

[22]  R. Margolis,et al.  Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase. , 2004, Molecular cell.

[23]  B. Paw,et al.  The pu.1 promoter drives myeloid gene expression in zebrafish. , 2004, Blood.

[24]  Nancy Hopkins,et al.  Identification of 315 genes essential for early zebrafish development. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Mikhailov,et al.  Topoisomerase II and histone deacetylase inhibitors delay the G2/M transition by triggering the p38 MAPK checkpoint pathway , 2004, The Journal of cell biology.

[26]  J. Maciejewski,et al.  Evolution Of Clonal Cytogenetic Abnormalities in Aplastic Anemia , 2004, Leukemia & lymphoma.

[27]  Nancy Hopkins,et al.  Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development , 2002, Nature Genetics.

[28]  J. Lukas,et al.  E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1 , 2002, Nature Cell Biology.

[29]  H. Hirai.  Molecular pathogenesis of MDS , 2002, International journal of hematology.

[30]  J. Peters,et al.  Emi1 Is a Mitotic Regulator that Interacts with Cdc20 and Inhibits the Anaphase Promoting Complex , 2001, Cell.

[31]  T. Gregory,et al.  Coincidence, coevolution, or causation? DNA content, cellsize, and the C‐value enigma , 2001, Biological reviews of the Cambridge Philosophical Society.

[32]  M. Lübbert,et al.  Allelic loss in the progression of myelodysplastic syndrome. , 2000, Cancer research.

[33]  A. Amsterdam,et al.  A large-scale insertional mutagenesis screen in zebrafish. , 1999, Genes & development.

[34]  W. Kuo,et al.  High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays , 1998, Nature Genetics.

[35]  Nancy Hopkins,et al.  Insertional mutagenesis and rapid cloning of essential genes in zebrafish , 1996, Nature.

[36]  C. Kimmel,et al.  Stages of embryonic development of the zebrafish , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[37]  D. J. Clarke,et al.  A topoisomerase II-dependent G2 cycle checkpoint in mammalian cells , 1994, Nature.

[38]  T. Andoh,et al.  Role of DNA topoisomerase II in chromosome dynamics in mammalian cells , 1993, Biotechnology and applied biochemistry.

[39]  D. J. Clarke,et al.  Topoisomerase II inhibition prevents anaphase chromatid segregation in mammalian cells independently of the generation of DNA strand breaks. , 1993, Journal of cell science.

[40]  T. Andoh,et al.  Inhibition of intracellular topoisomerase II by antitumor bis(2,6-dioxopiperazine) derivatives: mode of cell growth inhibition distinct from that of cleavable complex-forming type inhibitors. , 1991, Cancer research.

[41]  W. Alexander,et al.  Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Eμ-myc transgenic mice , 1991, Cell.