MUTATIONS OF THE DROSOPHILA DDP, DE2F, AND CYCLIN-E GENES REVEAL DISTINCT ROLES FOR THE E2F-DP TRANSCRIPTION FACTOR AND CYCLIN-E DURING THEG(1)-S TRANSITION

Activation of heterodimeric E2F-DP transcription factors can drive the G(1)-S transition. Mutation of the Drosophila melanogaster dE2F gene eliminates transcriptional activation of several replication factors a t the G(1)-S transition and compromises DNA replication, Here we descr ibe a mutation in the Drosophila dDP gene. As expected for a defect in the dE2F partner, this mutation blocks G(1)-S transcription of DmRNR2 and cyclin E as previously described for mutations of dE2F. Mutation of dDP also causes an incomplete block of DNA replication. When S phas e is compromised by reducing the activity of dE2F-dDP by either a dE2F or dDP mutation, the first phenotype detected is a reduction in the i ntensity of BrdU incorporation and a prolongation of the labeling. Not ably, in many cells, there was no detected delay in entry into this co mpromised S phase, In contrast, when cyclin E function was reduced by a hypomorphic allele combination, BrdU incorporation was robust but th e timing of S-phase entry was delayed. We suggest that dE2F-dDP contri butes to the expression of two classes of gene products: replication f actors, whose abundance has a graded effect on replication, and cyclin E, which triggers an all-or-nothing transition from G(1) to S phase.