Previously, five suppressors of the C. elegans
sel-12 presenilin gene have been identified in genetic screens. These genes encode components of a putative transcriptional repressor complex that normally represses the transcription of a second presenilin gene,
hop-1, and presumably other targets. The SPR proteins are similar to components of the human REST-CoREST complex, which represses the expression of certain neuronal genes in non-Neuronal cell types. We have been doing new screens to find additional components of this complex and other types of genes that can suppress
sel-12. In screens for
dog-1(
gk10) induced mutations (see abstract by Lakowski et al.), we have identified three small deletions in the
spr-3 gene, one allele of
spr-4 and three dominant spr mutations that may define one or more new genes. In a large-scale EMS screen for new spr mutations, we have recovered 44 mutations of varying phenotypic strength. This screen was done at 25C in the hope of finding some temperature sensitive (ts) mutations. Ts alleles can be very informative for studying the different biological roles of a gene and should greatly aid in characterising the spr genes. At least seven mutations appear to be ts. As expected, we have recovered new alleles of all previously identified spr genes. We also identified at least two new alleles of
sel-10, known to be a suppressor of
sel-12 (Wu et al., 1998). Additionally, we are characterizing several other mutations that may define at least three different new genes. At the meeting, we will present our progress towards cloning and characterising the new spr genes. Wu, G., Hubbard, E. J., Kitajewski, J. K. and Greenwald, I. (1998). Proc Natl Acad Sci U S A 95, 15787-91.