title: Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression.
abstract: The transactivation/transformation-domain associated protein (TRRAP) belongs to the Ataxia-telangiectasia mutated (ATM) super-family and has been identified as a cofactor for c-MYC-mediated oncogenic transformation. TRRAP and its yeast homolog (Tra1p) are components of histone acetyltransferase (HAT) complexes, SAGA (refs. 2,4,5), PCAF (ref. 3) and NuA4 (ref. 6), which are important for the regulation of transcription and cell cycle progression and also have a role in cell viability. Yet the biological function of this molecule and how it controls proliferation are still unclear. Here we show that null mutation of Trrap in mice results in peri-implantation lethality due to a blocked proliferation of blastocysts. We use an inducible Cre-loxP system to show that loss of Trrap blocks cell proliferation because of aberrant mitotic exit accompanied by cytokinesis failure and endoreduplication. Trrap-deficient cells fail to sustain mitotic arrest despite chromosome missegregation and disrupted spindles, and display compromised cdk1 activity. Trrap is therefore essential for early development and required for the mitotic checkpoint and normal cell cycle progression.
authors.affiliation: International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, F-69008, Lyon, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Herceg
authors.forename: W
authors.initials: W
authors.lastname: Hulla
authors.forename: D
authors.initials: D
authors.lastname: Gell
authors.forename: C
authors.initials: C
authors.lastname: Cuenin
authors.forename: M
authors.initials: M
authors.lastname: Lleonart
authors.forename: S
authors.initials: S
authors.lastname: Jackson
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D005313:Fetal Death / Q000235:genetics*; D005804:Genes, Lethal; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D009687:Nuclear Proteins; C113829:transformation-transcription domain-associated protein