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 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.

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.



Berube NG, Smeenk CA and Picketts DJ (2000) Cell cycle‐dependent phosphorylation of the ATRX protein correlates with changes in nuclear matrix and chromatin association. Human Molecular Genetics 9: 539–547.

Bergerat A, de Massy B, Gadelle D, et al. (1997) An atypical topoisomerase II from Archaea with implications for meiotic recombination. Nature 386: 414–417.

Champoux JJ (2001) DNA topoisomerases: structure, function, and mechanism. Annual Review of Biochemistry 70: 369–413.

Chong JP, Hayashi MK, Simon MN, Xu RM and Stillman B (2000) A double‐hexamer archaeal minichromosome maintenance protein is an ATP‐dependent DNA helicase. Proceedings of the National Academy of Sciences of the United States of America 97: 1530–1535.

De Boer J, Andresso JO, de Wit J, et al. (2002) Premature aging in mice deficient in DNA repair and transcription. Science 296(5571): 1276–1279.

Gangloff S, Soustelle C and Fabre F (2000) Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases. Nature Genetics 25: 192–194.

Gregg AV, McGlynn P, Jaktaji RP and Lloyd RG (2002) Direct rescue of stalled DNA replication forks via the combined action of PriA and RecG helicase activities. Molecular Cell 9: 241–251.

Hiramoto T, Nakanishi T, Sumiyoshi T, et al. (1999) Mutations of a novel human RAD54homologue, RAD54B, in primary cancer. Oncogene 18: 3422–3426.

Holm C, Stearns T and Botstein D (1989) DNA topoisomerase II must act at mitosis to prevent nondisjunction and chromosome breakage. Molecular Cell Biology 9: 159–168.

Keeney S, Giroux CN and Kleckner N (1997) Meiosis‐specific DNA double‐strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88: 375–384.

Labib K and Diffley JF (2001) Is the MCM2‐7 complex the eukaryotic DNA replication fork helicase?. Current Opinion in Genetics and Development 11: 64–70.

Matson SW and Kaiser‐Rogers KA (1990) DNA helicases. Annual Review of Biochemistry 59: 289–329.

Matsuda M, Miyagawa K, Takahashi M, et al. (1999) Mutations in the RAD54 recombination gene in primary cancers. Oncogene 18: 3427–3430.

Taylor EM, Broughton BC, Botta E, et al. (1997) Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD(ERCC2) repair/transcription gene. Proceedings of the National Academy of Sciences of the United States of America 94: 8658–8663.

Wang Y, Cortez D, Yazdi P, et al. (2000) BASC, a super complex of BRCA1‐associated proteins involved in the recognition and repair of aberrant DNA structures. Genes and Development 14: 927–939.

Wu L and Hickson ID (2001) RecQ helicases and topoisomerases: components of a conserved complex for the regulation of genetic recombination. Cellular and Molecular Life Sciences: CMLS 58: 894–901.

Further Reading

Berger SL and Felsenfeld G (2001) Chromatin goes global. Molecular Cell 8: 263–268.

Bochar DA, Wang L, Beniya H, et al. (2000) BRCA1is associated with a human SWI/SNF‐related complex: linking chromatin remodeling to breast cancer. Cell 102: 257–265.

Cairns BR (1998) Chromatin remodeling machines: similar motors, ulterior motives. Trends in Biochemical Sciences 23: 20–25.

Coin F, Marinoni JC, Rodolfo C, et al. (1998) Mutations in the XPDhelicase gene result in XP and TTD phenotypes, preventing interaction between XPDand the p44 subunit of TFIIH. Nature Genetics 20: 184–188.

Goedecke W, Eijpe M, Offenberg HH, van Aalderen M and Heyting C (1999) Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis. Nature Genetics 23: 194–198.

Ivessa AS, Zhou JQ and Zakian VA (2000) The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA. Cell 100: 479–489.

Liu M, Xie Z and Price DH (1998) A human RNA polymerase II transcription termination factor is a SWI2/SNF2 family member. Journal of Biological Chemistry 273: 25541–25544.

Shimamoto A, Nishikawa K, Kitao S and Furuichi Y (2000) Human RecQ5beta, a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerases III‐alpha and III‐beta. Nucleic Acids Research 28: 1647–1655.

Tanaka K, Hiramoto T, Fukuda T and Miyagawa K (2000) A novel human rad54 homologue, Rad54B, associates with Rad51. Journal of Biological Chemistry 275: 26316–26321.

Woodage T, Basrai MA, Baxevanis AD, Hieter P and Collins FS (1997) Characterization of the CHD family of proteins. Proceedings of the National Academy of Sciences of the United States of America 94: 11472–11477.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
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]