Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program.
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.
Royzman
I
I
Department of Biology, Massachusetts Institute of Technology, and Whitehead Institute, Cambridge 02142, USA.
Whittaker
A J
AJ
Orr-Weaver
T L
TL
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000235:genetics; D004261:DNA Replication; D004268:DNA-Binding Proteins; D019281:Dimerization; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005123:Eye / Q000254:growth & development; D005260:Female; D016193:G1 Phase / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007814:Larva; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011679:Pupa; D012333:RNA, Messenger / Q000032:analysis; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors