title: Identification and characterization of genes that interact with lin-12 in Caenorhabditis elegans.
abstract: We identified and characterized 14 extragenic mutations that suppressed the dominant egg-laying defect of certain lin-12 gain-of-function mutations. These suppressors defined seven genes: sup-17, lag-2, sel-4, sel-5, sel-6, sel-7 and sel-8. Mutations in six of the genes are recessive suppressors, whereas the two mutations that define the seventh gene, lag-2, are semi-dominant suppressors. These suppressor mutations were able to suppress other lin-12 gain-of-function mutations. The suppressor mutations arose at a very low frequency per gene, 10-50 times below the typical loss-of-function mutation frequency. The suppressor mutations in sup-17 and lag-2 were shown to be rare non-null alleles, and we present evidence that null mutations in these two genes cause lethality. Temperature-shift studies for two suppressor genes, sup-17 and lag-2, suggest that both genes act at approximately the same time as lin-12 in specifying a cell fate. Suppressor alleles of six of these genes enhanced a temperature-sensitive loss-of-function allele of glp-1, a gene related to lin-12 in structure and function. Our analysis of these suppressors suggests that the majority of these genes are part of a shared lin-12/glp-1 signal transduction pathway, or act to regulate the expression or stability of lin-12 and glp-1.
authors.affiliation: Department of Genetics, University of Washington, Seattle 98195, USA.
authors.forename: F E
authors.initials: FE
authors.lastname: Tax
authors.forename: J H
authors.initials: JH
authors.lastname: Thomas
authors.forename: E L
authors.initials: EL
authors.lastname: Ferguson
authors.forename: H R
authors.initials: HR
authors.lastname: Horvitz
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D009030:Mosaicism; D051880:Receptors, Notch; D013489:Suppression, Genetic; D013696:Temperature
chemical_list: D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D015801:Helminth Proteins; C082460:Lin-12 protein, C elegans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C086488:lag-2 protein, C elegans