HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Drosophila E2f2 promotes the conversion from genomic DNA replication to gene amplification in ovarian follicle cells.

Abstract
Drosophila contains two members of the E2F transcription factor family (E2f and E2f2), which controls the expression of genes that regulate the G1-S transition of the cell cycle. Previous genetic analyses have indicated that E2f is an essential gene that stimulates DNA replication. We show that loss of E2f2 is viable, but causes partial female sterility associated with changes in the mode of DNA replication in the follicle cells that surround the developing oocyte. Late in wild-type oogenesis, polyploid follicle cells terminate a program of asynchronous endocycles in which the euchromatin is entirely replicated, and then confine DNA synthesis to the synchronous amplification of specific loci, including two clusters of chorion genes that encode eggshell proteins. E2f2 mutant follicle cells terminate endocycles on schedule, but then fail to confine DNA synthesis to sites of gene amplification and inappropriately begin genomic DNA replication. This ectopic DNA synthesis does not represent a continuation of the endocycle program, as the cells do not complete an entire additional S phase. E2f2 mutant females display a 50% reduction in chorion gene amplification, and lay poorly viable eggs with a defective chorion. The replication proteins ORC2, CDC45L and ORC5, which in wild-type follicle cell nuclei localize to sites of gene amplification, are distributed throughout the entire follicle cell nucleus in E2f2 mutants, consistent with their use at many genomic replication origins rather than only at sites of gene amplification. RT-PCR analyses of RNA purified from E2f2 mutant follicle cells indicate an increase in the level of Orc5 mRNA relative to wild type. These data indicate that E2f2 functions to inhibit widespread genomic DNA synthesis in late stage follicle cells, and may do so by repressing the expression of specific components of the replication machinery.
AuthorsP Cayirlioglu, P C Bonnette, M R Dickson, R J Duronio
JournalDevelopment (Cambridge, England) (Development) Vol. 128 Issue 24 Pg. 5085-98 (Dec 2001) ISSN: 0950-1991 [Print] England
PMID11748144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Dp transcription factor, Drosophila
  • Drosophila Proteins
  • E2F Transcription Factors
  • E2F2 Transcription Factor
  • E2f2 protein, Drosophila
  • Trans-Activators
  • Transcription Factors
Topics
  • Animals
  • Cell Cycle Proteins
  • Chorion (growth & development)
  • DNA Replication
  • DNA-Binding Proteins (metabolism)
  • Drosophila (physiology)
  • Drosophila Proteins
  • E2F Transcription Factors
  • E2F2 Transcription Factor
  • Female
  • Fertility (genetics)
  • Gene Amplification
  • Mutagenesis
  • Mutation
  • Oogenesis (physiology)
  • Ovarian Follicle (cytology, physiology)
  • Penetrance
  • Protein Binding
  • S Phase (genetics)
  • Trans-Activators (metabolism)
  • Transcription Factors (genetics, metabolism)
  • Two-Hybrid System Techniques

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: