Abstract
BackgroundThe genetic code imposes a dilemma for cells. The DNA must be long enough to encode for the complexity of an organism, yet thin and flexible enough to fit within the cell. The combination of these properties greatly favors DNA collisions, which can knot and drive recombination of the DNA. Despite the well-accepted propensity of cellular DNA to collide and react with itself, it has not been established what the physiological consequences are.ResultsHere we analyze the effects of recombined and knotted plasmids in E. coli using the Hin site-specific recombination system. We show that Hin-mediated DNA knotting and recombination (i) promote replicon loss by blocking DNA replication; (ii) block gene transcription; and (iii) cause genetic rearrangements at a rate three to four orders of magnitude higher than the rate for an unknotted, unrecombined plasmid.ConclusionThese results show that DNA reactivity leading to recombined and knotted DNA is potentially toxic and may help drive genetic evolution.
Highlights
The genetic code imposes a dilemma for cells
For 200 kb DNA molecules at thermal equilibrium, the most energetically favorable conformation is the trefoil knot, 31 [5]. 200 kb is ~20-fold smaller than the chromosome of E. coli
We have shown previously that Hin recombines and knots plasmid DNA in E. coli that topoisomerase IV unties [21]
Summary
The DNA must be long enough to encode for the complexity of an organism, yet thin and flexible enough to fit within the cell. The combination of these properties greatly favors DNA collisions, which can knot and drive recombination of the DNA. The long (1.6 mm for Escherichia coli) and flexible (persistence length ≈ 50 nm) DNA must be compacted into a very small volume, achieving a liquid crystalline state of 80 – 100 mg/ml [2,3,4]. For 200 kb DNA molecules at thermal equilibrium, the most energetically favorable conformation is the trefoil knot, 31 [5]. It is not surprising that when cells are (page number not for citation purposes)
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