Mutations of the Drosophila dDP, dE2F, and cyclin E genes reveal distinct roles for the E2F-DP transcription factor and cyclin E during the G1-S transition

Mol Cell Biol. 1998 Jan;18(1):141-51. doi: 10.1128/MCB.18.1.141.

Abstract

Activation of heterodimeric E2F-DP transcription factors can drive the G1-S transition. Mutation of the Drosophila melanogaster dE2F gene eliminates transcriptional activation of several replication factors at the G1-S transition and compromises DNA replication. Here we describe a mutation in the Drosophila dDP gene. As expected for a defect in the dE2F partner, this mutation blocks G1-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 phase 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 intensity of BrdU incorporation and a prolongation of the labeling. Notably, in many cells, there was no detected delay in entry into this compromised S phase. In contrast, when cyclin E function was reduced by a hypomorphic allele combination, BrdU incorporation was robust but the timing of S-phase entry was delayed. We suggest that dE2F-dDP contributes to the expression of two classes of gene products: replication factors, whose abundance has a graded effect on replication, and cyclin E, which triggers an all-or-nothing transition from G1 to S phase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins*
  • Cell Cycle / genetics*
  • Cell Cycle Proteins*
  • Cyclin E / genetics*
  • DNA-Binding Proteins*
  • Drosophila Proteins*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • E2F Transcription Factors
  • G1 Phase
  • Genes, Insect
  • Molecular Sequence Data
  • Mutation*
  • Proteins / genetics*
  • Retinoblastoma-Binding Protein 1
  • S Phase
  • Trans-Activators*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin E
  • DNA-Binding Proteins
  • Dp transcription factor, Drosophila
  • Drosophila Proteins
  • E2F Transcription Factors
  • Proteins
  • Retinoblastoma-Binding Protein 1
  • Trans-Activators
  • Transcription Factors

Associated data

  • GENBANK/AF031700