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, sugg esting a negative role for E2F in controlling cell proliferation in so me 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-depen dent G(1)-S transcription, S-phase still occurs. Cyclin E has been sho wn to be essential for S-phase in late embryogenesis, but in dDP and d E2F mutants the peaks of G(1)-S transcription of cyclin E are missing. Thus, greatly reduced levels of cyclin E transcript suffice for DNA r eplication 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 promo te progression of the cell cycle.