CUL-1 IS REQUIRED FOR CELL-CYCLE EXIT IN C-ELEGANS AND IDENTIFIES A NOVEL GENE FAMILY

The gene cul-1 (formerly lin-19) is a negative regulator of the cell c ycle in C. elegans. Null mutations cause hyperplasia of all tissues. c ul-1 is required for developmentally programmed transitions from the G 1 phase of the cell cycle to the G0 phase or the apoptotic pathway. Mo reover, the mutant phenotype suggests that G1-to-S phase progression i s accelerated, overriding mechanisms for mitotic arrest and producing abnormally small cells. Significantly, diverse aspects of cell fate an d differentiation are unaffected in cul-1 mutants. cul-1 represents a conserved family of genes, designated cullins, with at least five memb ers in nematodes, six in humans, and three in budding yeast.