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

• Published in: Genes & development 2000-07, Vol.14 (14), p.1765-1776
• Main Authors: Whittaker, A J, Royzman, I, Orr-Weaver, T L
• Format: Article
• Language: English
• Subjects: AE2F protein; Alleles; Amino Acid Sequence; Animals; Bromodeoxyuridine - metabolism; Carrier Proteins; Cell Cycle Proteins; Cloning, Molecular; Conserved Sequence; Cyclin E - metabolism; cyclin F; DNA Replication; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; double parked (dup) gene; Down-Regulation; Drosophila; Drosophila - embryology; Drosophila - genetics; Drosophila Proteins; E2F protein; E2F Transcription Factors; Gene Expression Regulation, Developmental; Insect Proteins - chemistry; Insect Proteins - genetics; Insect Proteins - physiology; Mitosis; Molecular Sequence Data; Multigene Family; Mutation; Origin Recognition Complex; Phenotype; Recombinant Fusion Proteins - metabolism; Replication Origin; Research Paper; Retinoblastoma-Binding Protein 1; RNA, Messenger - metabolism; S Phase; Sequence Homology, Amino Acid; Trans-Activators; Transcription Factors - metabolism
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.14.14.1765

We identified a Drosophila gene, double parked (dup), that is essential for DNA replication and belongs to a new family of replication proteins conserved from Schizosaccharomyces pombe to humans. Strong mutations in dup 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 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 suggests 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. 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.