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I was reading DNA replication in E.coli in Lehninger Principles of Biochemistry 6th Ed. and stumbled upon the following --

The tight right handed wrapping of DNA around DnaA oligomeric complex induces an effective positive supercoil. The associated strain in the nearby DNA leads to denaturation of AT rich DUE region.

Edit:

Yet again I have come across the following in in Indian Molecular Biology books which certainly contradict Lehninger.

Binding of DnaA protein to oriC initiates unwinding of the DUE by introduction of negative superhelical turns.

I've done a little more research and found this paper, which clarifies the problem I previously had:

As a right-handed ATP-DnaA spiral would be expected to wrap DNA into a positive supercoil, adjacent DNA regions would be subjected to compensatory negative writhe (Fig. 6d, left). Although any superhelical strain generated by DnaA-mediated wrapping would be expected to spread throughout the topological domain that con- tains the origin, it may preferentially affect the nearby DUE, which is unstable and prone to spontaneous unwinding (Fig. 6d, top arrow).

enter image description here

Changed question: Why is this negative supercoiling generated in a positively supercoiling ccDNA?

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  • $\begingroup$ Not my area of expertise, but can you further explain the inconsistency/contradiction? I'm not seeing it. $\endgroup$
    – Bryan Krause ♦
    Dec 7, 2016 at 16:06
  • $\begingroup$ @BryanKrause Expecting that you are aware of DNA replication and supercoiling in general I put the issue in my words,one book says that DnaA protein forms an oligomeric complex and the DNA wraps around it in right handed fashion creating positive supercoils that denatures the weak A=T rich regions and that's where the rep. bubble is formed. The other book says that the DNA wraps around in left handed fashion underwinding the DUE(region rich in AT), not breaking them(remember) by producing negative supercoils. $\endgroup$
    – Tyto alba
    Dec 7, 2016 at 16:29
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    $\begingroup$ Again, not my area of expertise, but I think what is happening is that DNA is wrapping "more tightly than normal" around the oligomeric complex - this causes it to be wrapped "less tightly than normal" at the DUE region. The two books are describing the same process from two perspectives - one is the perspective of the protein, the other is the perspective of the DNA where transcription is taking place. $\endgroup$
    – Bryan Krause ♦
    Dec 7, 2016 at 17:13

1 Answer 1

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For a piece of topologically constrained DNA, Lk is constant. Since Lk = Wr + Tw, if you increase Wr in one area, it can be compensated by decreased Wr or Tw in an adjacent area. You may ask why the unwinding is concentrated in the adjacent region and not spread throughout. This is explained in the paper you link to:

Although any superhelical strain generated by DnaA-mediated wrapping would be expected to spread throughout the topological domain that contains the origin, it may preferentially affect the nearby DUE, which is unstable and prone to spontaneous unwinding.

The DNA unwinding element (DUE) is unstable because it is AT rich:

…the opening of individual AT/TA base pairs in the three DUEs investigated differs from that of GC/CG base pairs in at least two respects. First, the opening of AT/TA base pairs is significantly more favorable, kinetically and energetically, than that of GC/CG base pairs. Second, the opening of AT/TA base pairs is affected by long range effects of the DNA base sequences, whereas the opening of GC/CG is insensitive to the base sequence beyond that of nearest neighbors. The first difference confirms the earlier proposal that the high content of AT and TA base pairs is necessary to lower the stability and enhance the dynamics of the three DUE sites. The second difference suggests that the sequences of these AT and TA base pairs have been selected by evolution as a means to modulate the energetic stability of the three DUE sites according to their location and function in the origin of DNA replication.

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