QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cayirlioglu, P. Articles by Duronio, R. J. Search for Related Content PubMed PubMed Citation Articles by Cayirlioglu, P. Articles by Duronio, R. J.

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

¹ Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA
² Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
³ Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, NC 27599, USA
⁴ Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA

*Author for correspondence (e-mail: duronio{at}med.unc.edu)

Accepted September 24, 2001

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.

Key words: E2F2, E2F, Drosophila, Oogenesis, ORC, Cell cycle, Replication

This article has been cited by other articles:

				J. Sun, L. Smith, A. Armento, and W.-M. Deng Regulation of the endocycle/gene amplification switch by Notch and ecdysone signaling J. Cell Biol., September 8, 2008; 182(5): 885 - 896. [Abstract] [Full Text] [PDF]

				P. Cayirlioglu, W. O. Ward, S. C. Silver Key, and R. J. Duronio Transcriptional Repressor Functions of Drosophila E2F1 and E2F2 Cooperate To Inhibit Genomic DNA Synthesis in Ovarian Follicle Cells Mol. Cell. Biol., March 15, 2003; 23(6): 2123 - 2134. [Abstract] [Full Text] [PDF]