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Genetics, Vol. 168, 855-865, October 2004, Copyright © 2004
doi:10.1534/genetics.103.025965

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Drosophila Damaged DNA-Binding Protein 1 Is an Essential Factor for Development

Kei-ichi Takata*, Hideki Yoshida{dagger}, Masamitsu Yamaguchi{ddagger} and Kengo Sakaguchi*,1

* Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan
{dagger} Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, Tokyo 192-8577, Japan
{ddagger} Department of Applied Biology, Faculty of Textile Sciences, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

1 Corresponding author: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan.
E-mail: takatak{at}upmc.edu

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.




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