<i>fzr-1</i> and <i>lin-35</i>/Rb function redundantly to control cell proliferation in <i>C. elegans</i> as revealed by a nonbiased synthetic screen

Genes and Development - Tập 16 Số 4 - Trang 503-517 - 2002
David S. Fay1,2, Sean Keenan1,2, Min Han1,2
1Department of Molecular Biology, University of Wyo-ming, PO Box 3944, Laramie, WY 82071-3944, USA.
2Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology University of Colorado Boulder, Colorado 80309-0347 USA

Tóm tắt

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 withlin-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 identifiedfzr-1, a gene that synthetically interacts with lin-35to 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.

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