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fzr-1 and lin-35Rb function redundantly ... by a nonbiased synthetic screen
fzr-1 and lin-35/Rb function redundantly to control cell proliferation in C. elegans as revealed by a nonbiased synthetic screen.
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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.
Fay DS, Keenan S, Han M
Genes & development
2002-02-15 00:00
16
4
503-17
Amino Acid Sequence,Animals,Caenorhabditis elegans,Caenorhabditis elegans Proteins,Cell Cycle Proteins,Cell Division,Cell Lineage,F-Box Proteins,Fertility,Fungal Proteins,Genes, Lethal,Genes, Synthetic,Genetic Techniques,Heat,Helminth Proteins,Molecular Sequence Data,Multigene Family,Mutagenesis,Organ Specificity,Phenotype,Repressor Proteins,Sequence Alignment,Sequence Homology, Amino Acid,Species Specificity,Stress,Caenorhabditis elegans Proteins,Cell Cycle Proteins,F-Box Proteins,Fungal Proteins,Helminth Proteins,Repressor Proteins,fzr-1 protein, C elegans,lin-23 protein, C elegans,lin-35 protein, C elegans
Howard Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347, USA davidfayuwyoedu
Genes Dev.
NIGMS F32GM20029-01, NIGMS GM37869
0890-9369
10.1101/gad.952302
532
True
11850412
