The human cullin protein CUL-2 functions in a ubiquitin-ligase complex with the von Hippel–Lindau (VHL) tumour suppressor protein. Here we show that, in Caenorhabditis elegans, cul-2 is expressed in proliferating cells and is required at two distinct points in the cell cycle, the G1-to-S-phase transition and mitosis. cul-2 mutant germ cells undergo a G1-phase arrest that correlates with accumulation of CKI-1, a member of the CIP/KIP family of cyclin-dependent-kinase inhibitors. In cul-2 mutant embryos, mitotic chromosomes are unable to condense, leading to unequal DNA segregation, chromosome bridging and the formation of multiple nuclei.
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We thank the Caenorhabditis Genetics Center for C. elegans strains; Y. Kohara for cDNA clones; A. Golden for anti-AIR-1 antibody; R.J. Barstead for a cDNA library; M. Farmer, M. Fechheimer, P. Shen and H. Cai for technical advice; V. Ambros and J. Rothman for communicating results before publication; the Genome Sequencing Consortium for C. elegans genomic sequence and cosmids; T. Schedl for helpful discussions; C. Johnson and L. Liu for providing a second cul-2 deletion allele, which produced an identical phenotype to that produced by allele ek1; and M. Pagano, G. Seydoux and C. Norris for critical reading of the manuscript. This project was supported by NIH grant R01 GM55297 and HFSPO grant RG-229/98 (to E.T.K.).
Correspondence and requests for materials should be addressed to E.T.K. The cki-1 and cki-2 cDNA sequences have been deposited at GenBank under accession numbers AF179358 and AF179359, respectively.
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Feng, H., Zhong, W., Punkosdy, G. et al. CUL-2 is required for the G1-to-S-phase transition and mitotic chromosome condensation in Caenorhabditis elegans. Nat Cell Biol 1, 486–492 (1999). https://doi.org/10.1038/70272
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