by Roberto
Fig. 1. Electron micrograph of a replicative intermediate of the plasmid ColE1, after nicking with DNAse I. Source.
That plasmids are autonomous replicating elements and that they can serve as excellent cloning vectors are facts most certainly well-known to STC readers. However, I venture to guess that the same cannot be said about the historical details of the when, how, and why plasmids became the subject of intense study and the many important contributions that those studies provided to biology. That is one reason why I am strongly recommending a recent review, A Brief History of Plasmids, by Don Helinski and published in ASM's EcoSal Plus. (Many thanks to Christoph for pointing Don's review out to me.)
A second reason is much more personal. In the early 1970s, while I was an undergraduate working on DNA polymerase I, I became fascinated with plasmids. I saw them as ideal systems for studying the regulation of DNA replication. So, it was no surprise that when I started in the Ph.D. program at UCSD, I joined Don's lab to do my thesis. As the tools of recombinant DNA became available, we exploited them to define the basic working parts of plasmids, aiming to test the "replicon hypothesis" elaborated in the landmark 1963 paper of Jacob, Brenner and Cuzin. The lab's extreme excitement surrounding the rapid progress we made remains firmly planted in my mind. Reading Don's retelling of the events of those times allowed me to relive that excitement. In his words: "The advent of in vitro recombinant DNA technology in the early 1970s gave rise in the following years to a burst of information on plasmid DNA structure, including defining the essential elements for the initiation of replication and the circuitry for the control of plasmid copy number..." "...restriction endonuclease analysis of plasmids demonstrated that, in many but not all cases, the replication initiation protein could act in trans on a replication origin, allowing for the separation of the origin from the initiation gene and the maintenance of the covalently closed form of the origin fragment in a bacterium that also harbored a compatible plasmid carrying the initiation protein gene." Million thanks for writing this wonderful essay, Don!
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