Autoregulation of 2 micron circle gene expression provides a model for maintenance of stable plasmid copy levels

The yeast plasmid 2 micron circle actively maintains high but stable copy levels in the cell, even though the plasmid confers no selective advantage to its host. To address the mechanism by which stable copy control is achieved, we have examined the level of expression of the genes resident on the yeast plasmid 2 micron circle as a function of the presence of proteins encoded by the plasmid. We find that transcription of the site-specific recombinase gene, FLP, is repressed at least 100-fold by the concerted action of the products of two other plasmid genes, REP1 and REP2. In addition, these products repress transcription of the REP1 gene itself. These results can be formulated into a consistent model for plasmid copy control.