title: Drosophila damaged DNA-binding protein 1 is an essential factor for development.
abstract: The damaged DNA-binding protein (DDB) complex, thought to recognize (6-4) photoproducts and other lesions in DNA, has been implicated to have a role in global genomic nucleotide excision repair (NER) and E2F-1-mediated transcription. The complex consists of a heterodimer of p127 (DDB1) and p48 (DDB2), the latter also being known as XPE. We reported previously that in Drosophila expression of the DDB1 (D-DDB1) gene is controlled by the DRE/DREF system, and external injury to DNA is not essential for D-DDB1 function. In the present study of the function of D-DDB1 in a multicellular system, we prepared transgenic flies, which were knocked down for the D-DDB1 gene due to RNA interference (RNAi), and performed immunocytochemistry to ascertain the distribution of D-DDB1 in the eye imaginal disc. It was found to be abundant in the anterior of the morphogenetic furrow (MF). Whole-body overexpression of dsRNA of D-DDB1 in Drosophila using a GAL4-UAS targeted expression system induced melanotic tumors and caused complete lethality. When limited to the eye imaginal disc, a severe rough eye phenotype resulted. Correspondingly, all of the D-DDB1 gene knocked-out flies also died. D-DDB1 therefore appears to be an essential development-associated factor in a multicellular organism.
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan. takatak@upmc.edu
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Takata
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001973:Bromodeoxyuridine; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000254:growth & development* / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005804:Genes, Lethal; D008297:Male; D010641:Phenotype; D034622:RNA Interference; D012330:RNA, Double-Stranded; D011993:Recombinant Fusion Proteins; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012330:RNA, Double-Stranded; D011993:Recombinant Fusion Proteins; D004706:Endodeoxyribonucleases; C112206:DdbP1 protein, Drosophila; D001973:Bromodeoxyuridine