Drosophila Myb mutations cause a delayed G1/S progression and abnormal mitosis, including defects in chromosome condensation and segregation. J.R. Manak , N. Mitiku , J. Lipsick. Dept Pathology, Stanford Univ Sch Medicine, Stanford, CA.

   Vertebrates have three related Myb genes. c-Myb is required for hematopoiesis and when altered causes leukemias and lymphomas, A-Myb is required for spermatogenesis and mammary gland proliferation in mice, and B-Myb is expressed in all dividing cells and is essential for early embryonic development. When quiescent cells enter the cell cycle, B-Myb is expressed in late G1/early S and is directly regulated by the p16/cyclinD/ p107-p130/ E2F pathway along with other S phase genes. These results suggest that B-Myb may be a critical regulator of S phase entry or progression.
    Drosophila and other invertebrates have only a single Myb gene most closely related to B-Myb. Two temperature sensitive alleles of Drosophila Myb (Dm-Myb) have previously been isolated and were reported to affect the G2/M transition (Katzen, A. et al., Genes & Dev 12: 831-43, 1998). We have now isolated two apparent null alleles of Dm-Myb. These mutants are late third instar larval/ prepupal lethals. Imaginal disc cells in these mutants show a prolonged G1 phase with a compensatory decrease in G2, not an increase in G2 as predicted from previously published reports. In addition, there are an increased number of cells arrested in M phase with a defect in chromosome condensation. We also observe a dramatic increase in polyploidy and aneuploidy, the latter of which is a hallmark of cancer in vertebrate systems. Recently, it has been shown that chromosome condensation can occur even when DNA replication is abrogated (Yu, K. et al., Nature Cell Biology 2: 609-615, 2000). Taken together, our results therefore suggest that Dm-Myb is essential for both timely entrance into S phase as well as chromosome condensation and segregation.