Abstract
Plasmids, DNA (or rarely RNA) molecules which replicate in cells autonomously (independently of chromosomes) as non-essential genetic elements, play important roles for microbes grown under specific environmental conditions as well as in scientific laboratories and in biotechnology. For example, bacterial plasmids are excellent models in studies on regulation of DNA replication, and their derivatives are the most commonly used vectors in genetic engineering. Detailed mechanisms of replication initiation, which is the crucial process for efficient maintenance of plasmids in cells, have been elucidated for several plasmids. However, to understand plasmid biology, it is necessary to understand regulation of plasmid DNA replication in response to different environmental conditions in which host cells exist. Knowledge of such regulatory processes is also very important for those who use plasmids as expression vectors to produce large amounts of recombinant proteins. Variable conditions in large-scale fermentations must influence replication of plasmid DNA in cells, thus affecting the efficiency of recombinant gene expression significantly. Contrary to extensively investigated biochemistry of plasmid replication, molecular mechanisms of regulation of plasmid DNA replication in response to various environmental stress conditions are relatively poorly understood. There are, however, recently published studies that add significant data to our knowledge on relations between cellular stress responses and control of plasmid DNA replication. In this review we focus on plasmids derived from bacteriophage lambda that are among the best investigated replicons. Nevertheless, recent results of studies on other plasmids are also discussed shortly.
Highlights
Stable maintenance in the host cells is the most important process for any bacterial plasmid
Emergence of plasmid-less cells in a population of bacteria that originally carried plasmids is a serious disadvantage from the point of view of these extrachromosomal genetic elements, as cells devoid of plasmids usually grow faster than those bearing such 'additional' molecules
Since the structure of λ plasmids, basic functions of λ replication genes and mechanism of replication initiation from oriλ were reviewed recently [19,20,21,22], in this article we provide only basic information about initiation of λ DNA replication, which is necessary to understand regulatory mechanisms operating under various stress conditions
Summary
Stable maintenance in the host cells is the most important process for any bacterial plasmid. The heritable replication complex, which under standard laboratory conditions is a stable structure able to function for many cell generations, is disassembled relatively shortly after transfer of bacteria from 30 to 43°C [53] This disassembly was found to be dependent on GroEL and GroES heat shock proteins [53]. Effects of enhanced production of recombinant proteins on stability of ColE1-like plasmids in E. coli strains were reported previously [71], and more recent studies revealed that features of recombinant proteins produced in bacteria affect efficiency of plasmid maintenance [72] Molecular mechanisms of these regulations remain to be elucidated.
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