Genetic characterization of cytological region 77A-D harboring the Presenilin gene of Drosophila melanogaster

We performed a systematic lethal mutagenesis of the genomic region uncovere d by Df(3L)rdSC-co2 (cytological interval 77A-D) to isolate mutations in th e single known Presenilin (Psn) gene of Drosophila melanogaster. Because th is segment of chromosome III has not been systematically characterized befo re, inter se complementation testing of newly recovered mutants was carried out. A total of 79 lethal mutations were isolated, representing at least 1 7 lethal complementation groups, including one corresponding to the Psn gen e. Fine structure mapping of the genomic region surrounding the Psn transcr iption unit by transgenic rescue experiments allowed us to localize two of the essential loci together with Psn within an similar to 12-kb, genomic DN A region. One of these loci, located 3' to Psn, encodes a Drosophila protei n related to the yeast 60S ribosomal protein L10 precursor. We also determi ned which of the newly recovered lethal mutant groups correspond to previou sly isolated lethal P-element insertions, lethal inversion breakpoints, and lethal polo gene mutants. Point mutations were identified in all five reco vered Psn alleles, one of which results in a single amino acid substitution G-E at a conserved residue in the C-terminal cytoplasmic tail of the prote in, suggesting an important functional role for this C-terminal domain of P resenilin. In addition, some viable mutations were recovered in the screen, including new alleles of the clipped and inturned loci.