The 2 microm circle plasmid in Saccharomyces cerevisiae is a model for a stable, 
high-copy-number, extrachromosomal "selfish" DNA element. By combining a 
partitioning system and an amplification system, the plasmid ensures its stable 
propagation and copy number maintenance, even though it does not provide any 
selective advantage to its host. Recent evidence suggests that the partitioning 
system couples plasmid segregation to chromosome segregation. We now demonstrate 
an unexpected and unconventional role for the mitotic spindle in the 
plasmid-partitioning pathway. The spindle specifies the nuclear address of the 2 
microm circle and promotes recruitment of the cohesin complex to the 
plasmid-partitioning locus STB. Only the nuclear microtubules, and not the 
cytoplasmic ones, are required for loading cohesin at STB. In cells recovering 
from nocodazole-induced spindle depolymerization and G(2)/M arrest, cohesin-STB 
association can be established coincident with spindle restoration. This 
postreplication recruitment of cohesin is not functional in equipartitioning. 
However, normally acquired cohesin can be inactivated after replication without 
causing plasmid missegregation. In the mtw1-1 mutant yeast strain, the plasmid 
cosegregates with the spindle and the spindle-associated chromosomes; by 
contrast, a substantial number of the chromosomes are not associated with the 
spindle. These results are consistent with a model in which the spindle promotes 
plasmid segregation in a chromosome-linked fashion.