E2F-induced S phase requires cyclin E.
Both the heterodimeric transcription factor, E2F, and the G1 cyclin, cyclin E, are required for the G1-S transition at the start of the metazoan cell cycle. It has been established that cyclin E can act as an upstream activator of E2F. In addition to this action, we show here that cyclin E has an essential role in DNA replication distinct from activating E2F. We have created transgenic Drosophila capable of inducible, ectopic production of E2F activity. Simultaneous overexpression of both Drosophila E2F subunits, dE2F and dDP, in embryos stimulated the expression of multiple E2F-target genes including cyclin E, and also caused the initiation of S phase. Mutation of cyclin E prevented the initiation of S phase after overexpression of dE2F/dDP without affecting induction of target gene expression. Thus, E2F-directed transcription cannot bypass loss of cyclin E in Drosophila embryos.
Duronio
R J
RJ
Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.
Brook
A
A
Dyson
N
N
O'Farrell
P H
PH
D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D004625:Embryo, Nonmammalian / Q000737:chemistry; D000078404:Epidermal Cells; D016193:G1 Phase; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019076:Transgenes
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; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors