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 motor in Saccharomyces cerevisiae but is not essential for cell viability. We identified 20 genes whose products are specifically required by cell deficient for Cin8p. All are associated with mitotic roles and represent at least four different functional pathways. These include genes whose products act in two spindle motor pathways that overlap in function with Cin8p, the kinesin-related Kip1p pathway and the cytoplasmic dynein pathway. In addition, genes required for mitotic spindle checkpoint function and for normal microtubule stability were recovered. Mutant alleles of eight genes caused phenotypes similar to dyn1 (encodes the dynein heavy chain), including a spindle-positioning defect. We provide evidence that the products of these genes function in concept with dynein. Among the dynein pathway gene products, we found homologues of the cytoplasmic dynein intermediate chain, the p150Glued subunit of the dynactin complex, and human LIS-1, required for normal brain development. These findings illustrate the complex cellular interactions exhibited by Cin8p, a member of a conserved spindle motor family.
Geiser
J R
JR
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Schott
E J
EJ
Kingsbury
T J
TJ
Cole
N B
NB
Totis
L J
LJ
Bhattacharyya
G
G
He
L
L
Hoyt
M A
MA
D000595:Amino Acid Sequence; D002465:Cell Movement; D002467:Cell Nucleus / Q000648:ultrastructure; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics; D004398:Dyneins / Q000502:physiology; D004722:Endoribonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D016547:Kinesins; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000502:physiology*; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D008938:Mitosis; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus / Q000502:physiology*; D013696:Temperature
C075342:CIN8 protein, S cerevisiae; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C086450:JNM1 protein, S cerevisiae; C431747:KIP1 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D029701:Saccharomyces cerevisiae Proteins; D004722:Endoribonucleases; C499539:PAC1 protein, S cerevisiae; D004398:Dyneins; D016547:Kinesins