Originally published as Genetics Published Articles Ahead of Print on April 28, 2006.

Genetics, Vol. 173, 1377-1387, July 2006, Copyright © 2006
doi:10.1534/genetics.106.057976

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

Peter J. Neuburger¹, Kenneth J. Saville², Jue Zeng³, Kerrie-Ann Smyth⁴ and John M. Belote⁵

Department of Biology, Syracuse University, Syracuse, New York 13244

⁵ Corresponding author: Department of Biology, Syracuse University, 130 College Place, Syracuse, NY 13244.
E-mail: jbelote{at}syr.edu

Two dominant temperature-sensitive (DTS) lethal mutants of Drosophila melanogaster are Pros26¹ and Prosß2¹, 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 ß6 and ß2 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 Pros25^SuDTS [originally called Su(DTS)], a missense mutation in the gene encoding the 20S proteasome 2 subunit. Pros25^SuDTS acts in a dominant manner to rescue both Pros26¹ and Prosß2¹ 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. Pros25^SuDTS is a recessive polyphasic lethal at ambient temperatures. The effects of these mutants on larval neuroblast mitosis were also examined. While Prosß2¹ 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.

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