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

We identified a Drosophila gene, double parked (dup), that is essential for DNA replication and belongs to a new family of replication proteins conser ved from Schizosaccharomyces pombe to humans. Strong mutations in dup cause embryonic lethality, preceded by a failure to undergo S phase during the p ostblastoderm divisions. dup is required also for DNA replication in the ad ult ovary, establishing that dup 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 s uggests that DUP plays a direct role in DNA replication. The dup transcript is cell cycle regulated and is under the control of E2F and Cyclin E. Inte restingly, dup mutant embryos fail both to downregulate S phase genes and t o engage a checkpoint preventing mitosis until completion of S phase. This could be either because these events depend on progression of S phase beyon d the point blocked in the dup mutants or because DUP is needed directly fo r these feedback mechanisms.