title: Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability.
abstract: Vertebrates have three related Myb genes. The c-Myb protooncogene is required for definitive hematopoiesis in mice and when mutated causes leukemias and lymphomas in birds and mammals. The A-Myb gene is required for spermatogenesis and mammary gland proliferation in mice. The ubiquitously expressed B-Myb gene is essential for early embryonic development in mice and is directly regulated by the p16/cyclin D/Rb family/E2F pathway along with many critical S-phase genes. Drosophila has a single Myb gene most closely related to B-Myb. We have isolated two late-larval lethal alleles of Drosophila Myb. Mutant imaginal discs show an increased number of cells arrested in M phase. Mutant mitotic cells display a variety of abnormalities including spindle defects and increased polyploidy and aneuploidy. Remarkably, some mutant cells have an aberrant S- to M-phase transition in which replicating chromosomes undergo premature histone phosphorylation and chromosomal condensation. These results suggest that the absence of Drosophila Myb causes a defect in S phase that may result in M-phase abnormalities. Consistent with a role for Drosophila Myb during S phase, we detected Dm-Myb protein in S-phase nuclei of wild-type mitotic cells as well as endocycling cells, which lack both an M phase and cyclin B expression. Moreover, we found that the Dm-Myb protein is concentrated in regions of S-phase nuclei that are actively undergoing DNA replication. Together these findings imply that Dm-Myb provides an essential nontranscriptional function during chromosomal replication.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Room L216, 300 Pasteur Drive, Stanford, CA 94305-5324, USA.
authors.forename: J Robert
authors.initials: JR
authors.lastname: Manak
authors.forename: Nesanet
authors.initials: N
authors.lastname: Mitiku
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Lipsick
mesh_terms: D000782:Aneuploidy; D000818:Animals; D004261:DNA Replication / Q000235:genetics*; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D020570:Genes, myb / Q000235:genetics*; D007621:Karyotyping; D009154:Mutation; D011123:Polyploidy; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*
chemical_list: D020598:Proto-Oncogene Proteins c-myb