Survival strategies of the yeast plasmid two-micron circle

The multicopy yeast plasmid 2-micron circle uses a number of strategies to insure its persistence in its host. The plasmid confers no selective phenotype to the cell in which it is resident. Nonetheless, the plasmid is lost at less than 1 per 10(5) cell divisions during continuous exponential growth. We have determined that the plasmid persists at least in part due to the ability of the plasmid to amplify its mean copy number when its cellular copy level is low and to distribute plasmid molecules equally between mother and daughter cells at mitosis. We have found that amplification of plasmid copy number occurs by a novel mechanism in which site-specific recombination induces a transient shift in the mode of replication from theta to rolling circle. Equitable partitioning of plasmid molecules requires plasmid-encoded proteins and a centromere-like segment on the plasmid. We have accumulated evidence consistent with a model of partitioning in which the partitioning proteins form a transnuclear structure that is responsible for distributing plasmid molecules throughout the nucleus prior to cell division. In this chapter we describe evidence supporting the existence and mode of action of these two plasmid strategies and discuss the extent to which these strategies may be a pervasive facet of the biology of eukaryotic extrachromosomal elements.