SACCHAROMYCES-CEREVISIAE GENES REQUIRED IN THE ABSENCE OF THE CIN8-ENCODED SPINDLE MOTOR ACT IN FUNCTIONALLY DIVERSE MITOTIC PATHWAYS

Kinesin-related Cin8p is the most important spindle-pole-separating mo tor in Saccharomyces cerevisiae but is not essential for cell viabilit y. We identified 20 genes whose products are specifically required by cells deficient for Cin8p. All are associated with mitotic roles and r epresent at least four different functional pathways. These include ge nes whose products act in two spindle motor pathways that overlap in f unction with Cin8p, the kinesin-related Kip1p pathway and the cytoplas mic dynein pathway. In addition, genes required for mitotic spindle ch eckpoint function and for normal microtubule stability were recovered. Mutant alleles of eight genes caused phenotypes similar to dyn1 (enco des the dynein heavy chain), including a spindle-positioning defect. W e provide evidence that the products of these genes function in concer t with dynein. Among the dynein pathway gene products, we found homolo gues of the cytoplasmic dynein intermediate chain, the p150(Glued) sub unit of the dynactin complex, and human LIS-1, required for normal bra in development. These findings illustrate the complex cellular interac tions exhibited by Cin8p, a member of a conserved spindle motor family .