A Genetic Suppressor of Two Dominant Temperature-Sensitive Lethal Proteasome Mutants of Drosophila melanogaster Is Itself a Mutated Proteasome Subunit Gene

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Abstract
Two dominant temperature-sensitive (DTS) lethal mutants of Drosophila melanogaster are Pros261 and Prosβ21, previously known as DTS5 and DTS7. Heterozygotes for either mutant die as pupae when raised at 29°, but are normally viable and fertile at 25°. Previous studies have identified these as missense mutations in the genes encoding the β6 and β2 subunits of the 20S proteasome, respectively. In an effort to isolate additional proteasome-related mutants a screen for dominant suppressors of Pros261 was carried out, resulting in the identification of Pros25SuDTS [originally called Su(DTS)], a missense mutation in the gene encoding the 20S proteasome α2 subunit. Pros25SuDTS acts in a dominant manner to rescue both Pros261 and Prosβ21 from their DTS lethal phenotypes. Using an in vivo protein degradation assay it was shown that this suppression occurs by counteracting the dominant-negative effect of the DTS mutant on proteasome activity. Pros25SuDTS is a recessive polyphasic lethal at ambient temperatures. The effects of these mutants on larval neuroblast mitosis were also examined. While Prosβ21 shows a modest increase in the number of defective mitotic figures, there were no defects seen with the other two mutants, other than slightly reduced mitotic indexes.