title: The Drosophila melanogaster RAD54 homolog, DmRAD54, is involved in the repair of radiation damage and recombination.
abstract: The RAD54 gene of Saccharomyces cerevisiae plays a crucial role in recombinational repair of double-strand breaks in DNA. Here the isolation and functional characterization of the RAD54 homolog of the fruit fly Drosophila melanogaster, DmRAD54, are described. The putative Dmrad54 protein displays 46 to 57% identity to its homologs from yeast and mammals. DmRAD54 RNA was detected at all stages of fly development, but an increased level was observed in early embryos and ovarian tissue. To determine the function of DmRAD54, a null mutant was isolated by random mutagenesis. DmRADS4-deficient flies develop normally, but the females are sterile. Early development appears normal, but the eggs do not hatch, indicating an essential role for DmRAD54 in development. The larvae of mutant flies are highly sensitive to X rays and methyl methanesulfonate. Moreover, this mutant is defective in X-ray-induced mitotic recombination as measured by a somatic mutation and recombination test. These phenotypes are consistent with a defect in the repair of double-strand breaks and imply that the RAD54 gene is crucial in repair and recombination in a multicellular organism. The results also indicate that the recombinational repair pathway is functionally conserved in evolution.
authors.affiliation: Department of Radiation Genetics and Chemical Mutagenesis, MGC, Leiden University, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Kooistra
authors.forename: K
authors.initials: K
authors.lastname: Vreeken
authors.forename: J B
authors.initials: JB
authors.lastname: Zonneveld
authors.forename: A
authors.initials: A
authors.lastname: de Jong
authors.forename: J C
authors.initials: JC
authors.lastname: Eeken
authors.forename: C J
authors.initials: CJ
authors.lastname: Osgood
authors.forename: J M
authors.initials: JM
authors.lastname: Buerstedde
authors.forename: P H
authors.initials: PH
authors.lastname: Lohman
authors.forename: A
authors.initials: A
authors.lastname: Pastink
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D004527:Egg Proteins; D005123:Eye / Q000196:embryology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect / Q000235:genetics / Q000502:physiology; D007814:Larva / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008938:Mitosis / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011995:Recombination, Genetic / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004527:Egg Proteins; D009153:Mutagens; D012333:RNA, Messenger; D008741:Methyl Methanesulfonate; C108443:okr protein, Drosophila; D004265:DNA Helicases