Stable maintenance of an extrachromosomal selfish DNA

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DESCRIPTION (provided by applicant): The yeast plasmid 2 micron circle provides a simple model system to study the molecular mechanisms by which a 'benign parasite genome' optimizes its survival strategies without compromising the fitness of its host. The informational content and organization of the plasmid genome is designed for its stable maintenance in the population at a steady state copy number that does not strain the host metabolic machinery. One molecular component of this high copy self-propagation mechanism is a stability system that ensures equal distribution of replicated plasmid molecules to daughter cells during cell division. Two plasmid-encoded proteins, together with a cis-acting DNA sequence (called the STB locus), are essential for the normal operation of the stability system. In addition, host encoded factors may contribute towards equipartitioning of plasmids. The 2-micron circle has also devised an amplification system, which comes into operation only when there is a drop in copy number due to an occasional failure in equal segregation. Amplification is mediated by the Flp recombinase (Flp for flipping or inverting DNA), whose activity converts a single replication initiation event into a multiple copying mechanism, thus quickly restoring copy number. In this proposal, we describe experiments that attempt to shed light on how the plasmid and host encoded components interact to establish a functional stability system. We believe that some of the principles gleaned from this study will have global implications in the symbiotic relationships among host-parasite genomes in prokaryotes and eukaryotes.