In higher eukaryotes, the pre-replication complex (pre-RC) component Cdt1 is the 
major regulator in licensing control for DNA replication. The Cul4-DDB1-based 
ubiquitin ligase mediates Cdt1 ubiquitylation for subsequent proteolysis. During 
the initiation of chorion gene amplification, Double-parked (Dup), the 
Drosophila ortholog of Cdt1, is restricted to chorion gene foci. We found that 
Dup accumulated in nuclei in Cul4 mutant follicle cells, and the accumulation 
was less prominent in DDB1 mutant cells. Loss of Cul4 or DDB1 activity in 
follicle cells also compromised chorion gene amplification and induced ectopic 
genomic DNA replication. The focal localization of Orc2, a subunit of the origin 
recognition complex, is frequently absent in Cul4 mutant follicle cells. 
Therefore, Cul4 and DDB1 have differential functions during chorion gene 
amplification.