title: 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 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.
authors.affiliation: Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Whittaker
authors.forename: I
authors.initials: I
authors.lastname: Royzman
authors.forename: T L
authors.initials: TL
authors.lastname: Orr-Weaver
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019927:Cyclin E / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D018507:Gene Expression Regulation, Developmental; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008938:Mitosis; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D051738:Origin Recognition Complex; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018741:Replication Origin; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; C411983:DUP protein, Drosophila; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D019476:Insect Proteins; D051738:Origin Recognition Complex; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors; D001973:Bromodeoxyuridine