Telomere-like Linear Retroplasmids of Fusarium

Southern Methodist University, Dallas TX

Investigators

Abstract

Kennell The project is focused on the mechanism of replication of a novel group of mitochondrial plasmids that have features expected of genetic elements that are related to the progenitors of telomerase. Plasmids pFOXC1, pFOXC2 and pFOXC3 arerelated, double-stranded linear DNAs that reside in the filamentous fungus, Fusarium oxysporum, and represent the first reported linear, autonomously-replicating genetic elements that replicate via reverse transcription. An in vitro system will be developed to study the mechanism of reverse transcription associated with the pFOXC retroplasmids. Initial efforts are directed at characterizing plasmid replication intermediates in order to accurately synthesize RNA templates used in reconstituted ribonucleoprotein complexes for in vitro analysis. Once established, the in vitro system will be used to evaluate the mechanism of (-) strand cDNA synthesis and its relationship to the generation and maintenance of telomere-like repeats associated with the plasmids. The findings will contribute to the understanding of reactions catalyzed by reverse transcriptases and provide insight into the relationship between retroelements and telomerase as well as the evolution of linear DNAs. The ends of eukaryotic chromosomes, termed telomeres, are maintained by enzyme complexes which contain a protein (reverse transcriptase) and an RNA component. It is widely speculated that these complexes, or telomerases, were derived from invasive genetic elements that encode reverse transcriptase. Previously, however, no genetic element has been identified that has structural and other features expected of a candidate progenitor that may have given rise to telomerase. This project seeks to elucidate the mechanism of replication of a novel group of mitochondrial plasmids that have features expected of genetic elements that are related to the progenitors of telomerase. Plasmids pFOXC1, pFOXC2 and pFOXC3 are related, double-stranded linear DNAs that reside in the filamentous fungus, Fusarium oxysporum, and represent the first reported linear, autonomously-replicating genetic elements that replicate via reverse transcription. Research involves the development of a system to study the mechanism of reverse transcription associated with the pFOXC retroplasmids and will provide insight into the relationship between retroelements and telomerase as well as the evolution of linear DNAs.