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Nature Cell Biology 1, 486–492 (1 December 1999) | doi:10.1038/70272

CUL-2 is required for the G1-to-S-phase transition and mitotic chromosome condensation in Caenorhabditis elegans

Hui Feng , Weiwei Zhong , George Punkosdy , Subin Gu , Liang Zhou , Erin K. Seabolt & Edward T. Kipreos

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.