Mutations in Drosophila DP and E2F distinguish G 1 –S progression from an associated transcriptional program

The E2F transcription factor, a heterodimer of E2F and DP subunits, is capable of driving the G 1 –S transition of the cell cycle. However, mice in which the E2F-1 gene had been disrupted developed tumors, suggesting a negative role for E2F in controlling cell proliferation in some tissues. The consequences of disrupting the DP genes have not been reported. We screened for mutations that disrupt G 1 –S transcription late in Drosophila embryogenesis and identified five mutations in the dDP gene. Although mutations in dDP or dE2F nearly eliminate E2F-dependent G 1 –S transcription, S-phase still occurs. Cyclin E has been shown to be essential for S-phase in late embryogenesis, but in dDP and dE2F mutants the peaks of G 1 –S transcription of cyclin E are missing. Thus, greatly reduced levels of cyclin E transcript suffice for DNA replication until late in development. Both dDP and dE2F are necessary for viability, and mutations in the genes cause lethality at the late larval/pupal stage. The mutant phenotypes reveal that both genes promote progression of the cell cycle.