The partitioning and copy number control systems of the selfish yeast plasmid: An optimized molecular design for stable persistence in host cells

The multicopy 2-micron plasmid of Saccharomyces cerevisiae, a resident of the nucleus, is remarkable for its high chromosome-like stability. The plasmid does not appear to contribute to the fitness of the host, nor does it impose a significant metabolic burden on the host at its steady state copy number. The plasmid may be viewed as a highly optimized selfish DNA element whose genome design is devoted entirely to efficient replication, equal segregation, and copy number maintenance. A partitioning system comprised of two plasmid-coded proteins, Rep1 and Rep2, and a partitioning locus, STB, is responsible for equal or nearly equal segregation of plasmid molecules to mother and daughter cells. Current evidence supports a model in which the Rep-STB system promotes the physical association of the plasmid with chromosomes and thus plasmid segregation by a hitchhiking mechanism. The Flp site-specific recombination system housed by the plasmid plays a critical role in maintaining a steady state plasmid copy number. A decrease in plasmid population due to rare missegregation events is rectified by plasmid amplification via a recombination-induced rolling circle-like replication mechanism. Appropriate plasmid amplification, without a runaway increase in copy number, is ensured by positive and negative regulation of FLP gene expression by plasmid-coded proteins and by the control of Flp level/activity through host-mediated posttranslational modification(s) of Flp. The Flp system has been successfully utilized to understand mechanisms of site-specific recombination, to bring about directed genetic alterations for addressing fundamental problems in biology, and as a tool in biotechnological applications.