Identification of new genes required for the maintenance of chromosome integrity in Drosophila melanogaster

Authors: FRANCESCA CEPRANI, FRANCO SPIRITO, ROBERTO PIERGENTILI

Abstract: Although genome-wide RNA interference (RNAi) screens for mitotic genes are not new in the literature, most of them lack the cytological characterization of the cell karyotype as for chromosome integrity. Here, the effects of RNAi on chromosome structure in S2 cultured cells of Drosophila melanogaster were analyzed. The cytological phenotype of 1132 genes selected by coexpression with known mitotic genes was scored. Cytological and statistical analysis of the treated cells allowed the identifying of 81 loci whose inactivation brings a level of chromosome breakage significantly higher than in the control. Many of the genes characterized in the present work had never been associated with a cellular function; in other cases, their putative role is apparently unrelated to the chromosome breakage phenotype. These results suggest novel biological roles for the proteins encoded by the identified genes and indicate that the number of loci required for chromosome integrity is much larger than expected. Moreover, these results strongly suggest that the compilation of a list of coexpressed genes for any given function would result in a largely incomplete set of data, and that quite surprisingly a more complete collection of loci may be obtained using screening criteria different from selection.

Keywords: Cancer, functional coexpression, genome instability, karyotype, S2 cultured cells, segmental aneuploidy, RNAi

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