Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program.

Department of Biology, Massachusetts Institute of Technology, and Whitehead Institute, Cambridge 02142, USA.
The E2F transcription factor, a heterodimer of E2F and DP subunits, is capable of driving the G1-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 G1-S transcription late in Drosophila embryogenesis and identified five mutations in the dDP gene. Although mutations in dDP or dE2F nearly eliminate E2F-dependent G1-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 G1-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.
Mesh Terms:
Amino Acid Sequence, Animals, Carrier Proteins, Cell Cycle Proteins, Cyclins, DNA Replication, DNA-Binding Proteins, Dimerization, Drosophila, Drosophila Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Eye, Female, G1 Phase, Gene Expression Regulation, Developmental, Larva, Male, Molecular Sequence Data, Phenotype, Point Mutation, Proliferating Cell Nuclear Antigen, Pupa, RNA, Messenger, Retinoblastoma-Binding Protein 1, S Phase, Trans-Activators, Transcription Factors, Transcription, Genetic
Genes Dev. Aug. 01, 1997; 11(15);1999-2011 [PUBMED:9271122]
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