DNA Coiling and Unwinding


The double‐helical structure of DNA and its higher orders of coiling are tightly controlled by two classes of enzyme, helicases and topoisomerases. These are part of large protein complexes that control the main DNA transactions within the cell. In humans, defects in these enzymes may result in various diseases.

Keywords: DNA supercoiling; topoisomerase; helicase; unwinding

Figure 1.

Unwinding the double helix. Separation of DNA strands needs the cooperation of two enzymatic activities: a helicase that breaks hydrogen bonding between bases, and a topoisomerase that removes strand intertwinings produced by the progression of the helicase. Two classes of topoisomerase may be involved: topoisomerases IB, which perform transient single‐strand breaks followed by rotation to remove the stress, and resealing; and topoisomerases II, which perform double‐strand breaks followed by passage of another DNA segment through the break, and resealing.

Figure 2.

Involvement of DNA supercoiling and unwinding in DNA transactions. Replication, recombination and chromosome segregation, transcription, and repair modify the helical twist or the writhe of the DNA, locally or globally, producing supercoiling. Helicases and topoisomerases regulate these structural changes. In eukaryotes, where DNA is packaged into chromatin, topoisomerases and possibly helicases play an additional role: by controlling DNA supercoiling and unwinding, they are able to regulate the accessibility of protein machineries to DNA.

Figure 3.

Chromatin remodeling. This hypothetical model is based on the assumption that chromatin remodeling machines have a ‘true’ helicase activity sustained by one of their subunits. Nucleosome stability is favored in a region of negative stress, because this stress (negative supercoils) is convertible to a left‐handed wrapping around the histone octamer (see inset). A promoter inside the nucleosome is supposed to be ‘off’. Thus a positive stress produced ahead of any helicase tracking through the DNA would destabilize the nucleosome and make the promoter accessible to the transcription machine. In the same way, the negative stress behind the helicase would restore the nucleosomal structure.

Figure 4.

Chromosome map. The various human genes potentially involved in DNA coiling and unwinding are positioned on the schematic chromosomes. Dark gray vertical bars correspond to putative DNA helicases, gray vertical bars to topoisomerases.

Figure 5.

Topoisomerases and helicases in transcription. Three potential roles are depicted: the progression of RNA polymerase (RNA pol II), facilitated by a first helicase (H1) generates topological constraints which are removed by topoisomerases I and II. Formation of a hybrid between nascent RNA and the template DNA strand produces the displacement of the other strand and gives a structure called the R‐loop. A helicase (H2) acting with topoisomerase I can remove this structure. Finally, the topoisomerase I‐specific kinase activity may phosphorylate the SR proteins at the splice sites.

Figure 6.

Unwinding and untangling DNA at the replication fork. The replicative helicase progresses through the DNA duplex by removing hydrogen bonds between bases. This needs the rotation of parental strands at a high rate. This rotation is compensated in two ways: in front of the helicase, topoisomerase I (and possibly topoisomerase II) relaxes the DNA overwinding (positive supercoiling), while, behind the fork, topoisomerase II suppresses tangles between the two daughter DNA duplexes.

Figure 7.

Helicases and topoisomerases in recombination. (a) Recombination events at arrested fork. When the replication complex is blocked on the leading strand (i.e. at a lesion), the replicative helicase may continue to open the duplex, providing a substrate for recombination. The polymerase may switch to copy the other newly replicated strand, producing a Holliday junction that could be further processed. This event presumably needs the cooperation of helicase and topoisomerase, for instance, a RecQ–topoIII complex, in addition to several other proteins such as Rad51, the equivalent of RecA in eukaryotes. (b) Two possible pathways for the behavior of recombination intermediates: disruption of the intermediate (left) which leads to repression of recombination, or branch migration (right) which favors recombination. In both cases, a helicase and a topoisomerase might be able to cooperate.



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Further Reading

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Hugodot, Yannick, and Duguet, Michel(Jan 2006) DNA Coiling and Unwinding. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005967]