title: CSN5/Jab1 mutations affect axis formation in the Drosophila oocyte by activating a meiotic checkpoint.
abstract: The COP9 signalosome (CSN) is linked to signaling pathways and ubiquitin-dependent protein degradation in yeast, plant and mammalian cells, but its roles in Drosophila development are just beginning to be understood. We show that during oogenesis CSN5/JAB1, one subunit of the CSN, is required for meiotic progression and for establishment of both the AP and DV axes of the Drosophila oocyte. The EGFR ligand Gurken is essential for both axes, and our results show that CSN5 mutations block the accumulation of Gurken protein in the oocyte. CSN5 mutations also cause the modification of Vasa, which is known to be required for Gurken translation. This CSN5 phenotype - defective axis formation, reduced Gurken accumulation and modification of Vasa - is very similar to the phenotype of the spindle-class genes that are required for the repair of meiotic recombination-induced, DNA double-strand breaks. When these breaks are not repaired, a DNA damage checkpoint mediated by mei-41 is activated. Accordingly, the CSN5 phenotype is suppressed by mutations in mei-41 or by mutations in mei-W68, which is required for double strand break formation. These results suggest that, like the spindle-class genes, CSN5 regulates axis formation by checkpoint-dependent, translational control of Gurken. They also reveal a link between DNA repair, axis formation and the COP9 signalosome, a protein complex that acts in multiple signaling pathways by regulating protein stability.
authors.affiliation: Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley 94720, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Doronkin
authors.forename: Inna
authors.initials: I
authors.lastname: Djagaeva
authors.forename: Steven K
authors.initials: SK
authors.lastname: Beckendorf
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004330:Drosophila / Q000166:cytology* / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008540:Meiosis / Q000235:genetics*; D008954:Models, Biological; D046912:Multiprotein Complexes; D009154:Mutation; D009865:Oocytes / Q000166:cytology*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D010447:Peptide Hydrolases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D016211:Transforming Growth Factor alpha; D015291:Transforming Growth Factors / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; C083730:grk protein, Drosophila; D015291:Transforming Growth Factors; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D010447:Peptide Hydrolases; C501491:CSN5 protein, Drosophila; D000075686:COP9 Signalosome Complex