Drosophila Double parked: a conserved, essential replication protein that colocalizes with the origin recognition complex and links DNA replication with mitosis and the down-regulation of S phase transcripts

Abstract

We identified a Drosophila gene, double parked(dup), that is essential for DNA replication and belongs to a new family of replication proteins conserved fromSchizosaccharomyces pombe to humans. Strong mutations indup cause embryonic lethality, preceded by a failure to undergo S phase during the postblastoderm divisions. dup is required also for DNA replication in the adult ovary, establishing thatdup is needed for DNA replication at multiple stages of development. Strikingly, DUP protein colocalizes with the origin recognition complex to specific sites in the ovarian follicle cells. This suggests that DUP plays a direct role in DNA replication. Thedup transcript is cell cycle regulated and is under the control of E2F and Cyclin E. Interestingly, dup mutant embryos fail both to downregulate S phase genes and to engage a checkpoint preventing mitosis until completion of S phase. This could be either because these events depend on progression of S phase beyond the point blocked in the dup mutants or because DUP is needed directly for these feedback mechanisms.

Keywords

• DNA replication
• amplification
• cell cycle
• Cdt1
• E2F