Recent findings in Drosophila have shown that 1) a significant proportion of spontaneous mutations are caused by insertions of mobile genetic elements, and 2) in certain genetic suppressor systems, suppressible alleles are caused by insertions of specific mobile elements. We are investigating the molecular mechanism of action of one such suppressor system: recessive mutations at the suppressor-of-sable (su(s)) locus suppress recessive mutations at the vermilion (v) locus that are caused by insertions of the mobile elements 412. Current results suggest that this suppression occurs pretranslationally. DNA sequences of su(s) have been cloned and are being characterized. An 8 kb segment of genomic DNA genes rise to a 5 kb poly A+ RNA that consists of at least 5 exons. All of fourteen su(s) mutations that are caused by insertions of various mobile elements have these insertions in a 2.2 segment of largely intronic genomic DNA that gives rise to the 5' end of the message. Open reading frame segments from the two largest exons have been ligated into expression vectors to produce fusion proteins against which antibodies have been produced. Antibodies against the su(s) portion of the fusion protein are being recovered and are being used as probes to identify the location and function of the su(s) protein within the organism. Wild type su(s) sequences have been introduced into su(s) mutant flies by P element transformation and they confer the wild type phenotype on these flies. These P element constructs will also be used to determine the effect of the su(s) protein product on the biology of the mobile element 412. The DNA of the region is being sequenced to determine the structure and regulation of the su(s) locus.
