We isolated mutations in Drosophila E2F and DP that affect chorion gene amp
lification and ORC2 localization in the follicle cells. In the follicle cel
ls of the ovary, the ORC2 protein is localized throughout the follicle cell
nuclei when they are undergoing polyploid genomic replication, and its lev
els appear constant in both S and G phases. In contrast, when genomic repli
cation ceases and specific regions amplify, ORC2 is present solely at the a
mplifying loci. Mutations in the DNA-binding domains of dE2F or dDP reduce
amplification, and in these mutants specific localization of ORC2 to amplif
ication loci is lost. Interestingly, a dE2F mutant predicted to lack the ca
rboxy-terminal transcriptional activation and RE-binding domain does not ab
olish ORC2 localization and shows premature chorion amplification. The effe
ct of the mutations in the heterodimer subunits suggests that E2F controls
not only the onset of S phase but also origin activity within S phase.