title: fzr-1 and lin-35/Rb function redundantly to control cell proliferation in C. elegans as revealed by a nonbiased synthetic screen.
abstract: We report here a synthetic-lethal screen in Caenorhabditis elegans that overcomes a number of obstacles associated with the analysis of functionally redundant genes. Using this approach, we have identified mutations that synthetically interact with lin-35/Rb, a SynMuv gene and the sole member of the Rb/pocket protein family in C. elegans. Unlike the original SynMuv screens, our approach is completely nonbiased and can theoretically be applied to any situation in which a mutation fails to produce a detectable phenotype. From this screen we have identified fzr-1, a gene that synthetically interacts with lin-35 to produce global defects in cell proliferation control. fzr-1 encodes the C. elegans homolog of Cdh1/Hct1/FZR, a gene product shown in other systems to regulate the APC cyclosome. We have also uncovered genetic interactions between fzr-1 and a subset of class B SynMuv genes, and between lin-35 and the putative SCF regulator lin-23. We propose that lin-35, fzr-1, and lin-23 function redundantly to control cell cycle progression through the regulation of cyclin levels.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347, USA. davidfay@uwyo.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Fay
authors.forename: Sean
authors.initials: S
authors.lastname: Keenan
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D044783:F-Box Proteins; D005298:Fertility / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D005804:Genes, Lethal; D005813:Genes, Synthetic; D005821:Genetic Techniques; D015801:Helminth Proteins / Q000502:physiology; D006358:Hot Temperature; D008969:Molecular Sequence Data; D005810:Multigene Family; D016296:Mutagenesis; D009928:Organ Specificity; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D005656:Fungal Proteins; D015801:Helminth Proteins; D012097:Repressor Proteins; C451030:fzr-1 protein, C elegans; C418507:lin-23 protein, C elegans; C116485:lin-35 protein, C elegans