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Genetics, Vol. 168, 1293-1306, November 2004, Copyright © 2004
doi:10.1534/genetics.104.029827
The Identities of sym-2, sym-3 and sym-4, Three Genes That Are Synthetically Lethal With mec-8 in Caenorhabditis elegans
John Yochem1, Leslie R. Bell and Robert K. Herman
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455
1 Corresponding author: Department of Genetics, Cell Biology, and Development, University of Minnesota, Room 6-160, Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455.
E-mail: jyochem{at}cbs.umn.edu
On the basis of synthetic lethality, five genes in Caenorhabditis elegans are known to be redundant with the mec-8 gene, which encodes a protein that contains two copies of an RNA recognition motif (RRM) and affects alternative RNA splicing. The molecular identities of two of the redundant genes, sym-1 and sym-5, were previously reported. The remaining three genes have now been cloned, and their synthetically lethal phenotypes with mec-8 are described in more detail. Animals homozygous for mec-8 and sym-2 loss-of-function mutations die during late embryogenesis. The SYM-2 predicted protein contains three RRMs; we propose that SYM-2 and MEC-8 can substitute for each other in promoting the maturation of the transcripts of a vital gene. Animals homozygous for mutations in mec-8 and in either sym-3 or sym-4 have the same striking defect: they arrest development just prior to or just after hatching with a pharynx that appears fully formed but is not properly attached to the body cuticle. sym-3 encodes a protein of unknown function with orthologs in Drosophila and mammals. sym-4 encodes a WD-repeat protein and may also have orthologs in Drosophila and mammals. We propose that SYM-3 and SYM-4 contribute to a common developmental pathway that is redundant with a MEC-8-dependent pathway.
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