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Originally published as Genetics Published Articles Ahead of Print on December 1, 2008.
Genetics, Vol. 181, 367-377, February 2009, Copyright © 2009
doi:10.1534/genetics.108.097345
HorkaD, a Chromosome Instability-Causing Mutation in Drosophila, Is a Dominant-Negative Allele of lodestar
Tamas Szalontai*,
Imre Gaspar*,
Istvan Belecz*,
Iren Kerekes*,
Miklos Erdelyi
,
Imre Boros
and
Janos Szabad*,1
* Department of Biology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary,
Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, H-6726 Szeged, Hungary and
Department of Biochemistry and Molecular Biology, University of Szeged, H-6726 Szeged, Hungary
1 Corresponding author: Department of Biology, Faculty of Medicine, University of Szeged, Somogyi Str. 4, H-6720 Szeged, Hungary.
E-mail: szabad{at}mdbio.szote.u-szeged.hu
Correct segregation of chromosomes is particularly challenging during the rapid nuclear divisions of early embryogenesis. This process is disrupted by HorkaD, a dominant-negative mutation in Drosophila melanogaster that causes female sterility due to chromosome tangling and nondisjunction during oogenesis and early embryogenesis. HorkaD 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 HorkaD-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 HorkaD mutation is lodestar, a member of the helicase-related genes. The HorkaD mutation results in replacement of Ala777 with Thr, which we suggest causes chromosome instability by increasing the affinity of Lodestar for chromatin.