title: HorkaD, a chromosome instability-causing mutation in Drosophila, is a dominant-negative allele of Lodestar.
abstract: Correct segregation of chromosomes is particularly challenging during the rapid nuclear divisions of early embryogenesis. This process is disrupted by Horka(D), a dominant-negative mutation in Drosophila melanogaster that causes female sterility due to chromosome tangling and nondisjunction during oogenesis and early embryogenesis. Horka(D) also renders chromosomes unstable during spermatogenesis, which leads to the formation of diplo//haplo mosaics, including the gynandromorphs. Complete loss of gene function brings about maternal-effect lethality: embryos of the females without the Horka(D)-identified gene perish due to disrupted centrosome function, defective spindle assembly, formation of chromatin bridges, and abnormal chromosome segregation during the cleavage divisions. These defects are indicators of mitotic catastrophe and suggest that the gene product acts during the meiotic and the cleavage divisions, an idea that is supported by the observation that germ-line chimeras exhibit excessive germ-line and cleavage function. The gene affected by the Horka(D) mutation is lodestar, a member of the helicase-related genes. The Horka(D) mutation results in replacement of Ala777 with Thr, which we suggest causes chromosome instability by increasing the affinity of Lodestar for chromatin.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, H-6726 Szeged, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Szalontai
authors.forename: Imre
authors.initials: I
authors.lastname: Gaspar
authors.forename: Istvan
authors.initials: I
authors.lastname: Belecz
authors.forename: Iren
authors.initials: I
authors.lastname: Kerekes
authors.forename: Miklos
authors.initials: M
authors.lastname: Erdelyi
authors.forename: Imre
authors.initials: I
authors.lastname: Boros
authors.forename: Janos
authors.initials: J
authors.lastname: Szabad
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D043171:Chromosomal Instability; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004527:Egg Proteins / Q000737:chemistry / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D017344:Genes, Insect; D005804:Genes, Lethal; D008297:Male; D008540:Meiosis / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009866:Oogenesis / Q000235:genetics; D010641:Phenotype; D013091:Spermatogenesis / Q000235:genetics; D018183:Transplantation Chimera / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004527:Egg Proteins; C071248:lds protein, Drosophila; C108443:okr protein, Drosophila; D004265:DNA Helicases