Stress responses and replication of plasmids in bacterial cells

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.

Figure 1

Replication region of bacteriophage λ genome and assembly of the replication complex. Genes, promoters and terminators present in the replication region are indicated. Transcripts are represented by arrows. The scheme is not drawn to scale. See text for details.

Figure 2

Two pathways of λ plasmid replication. Large circles represent plasmid DNA molecules. Small filled (orange) circles indicate heritable λ replication complexes. See text for details.

Figure 3

Effects of various factors on formation and stability of the λ heritable replication complex. The complex is symbolized by large orange circle. Positive regulators are marked in green, and negative regulators are marked in blue. Stimulation processes are shown as arrows and inhibitory actions are shown by blunt-ended lines. See text for details.