DNA Structure: Sequence Effects

Abstract

Deoxyribonucleic acid (DNA) sequence significantly affects the local stability of the DNA double helix. Two types of stability of the DNA duplex must be distinguished: thermodynamic stability and kinetic stability. Although stability of the DNA region depends mostly on its G•C content, it is stacking interaction between adjacent base pairs which have dominating contribution into the overall region stability. Sequence effects play especially important role in the stability of DNA helices different from B‐ and A‐forms such as Z‐DNA, parallel duplex, triplexes and quadruplexes. Depending on their particular sequence, different DNA sites are capable of adopting various unusual structures, among them: the cruciform, the triplex H form, the Z form and quadruplexes. These sequence‐dependent structures are stabilized by DNA negative supercoiling. They attract more and more attention in recent years because of their potential as targets for anticancer drugs and as tools in bio‐ and nanotechnology.

Key Concepts:

  • DNA thermodynamic stability determines equilibrium properties of the double helix but equilibrium is not always achievable.

  • DNA kinetic stability governs DNA behaviour at the characteristic time of experiment.

  • Stacking interactions, rather than base pairing, play the decisive role in determining the stability of the DNA double helix.

  • Highly sequence‐dependent DNA unusual structures dramatically affect DNA structural variability.

  • Unusual structures are thermodynamically unfavourable in linear DNA but their formation becomes possible in negatively supercoiled DNA.

Keywords: DNA melting; DNA unusual structures; Gibbs free energy; kinetic stability; supercoiling; thermodynamic stability

Figure 1.

Schematics of (a) B‐DNA and some of DNA unusual structures; (b) Z‐DNA; (c) intermolecular triplex; (d) cruciform; (e) H‐DNA and (f) G‐quadruplex and its various folding modes.

Figure 2.

DNA base triads. (a) The Hoogsteen base triads. The Watson–Crick and Hoogsteen pairings are indicated by arrows. Note that to form the Hoogsteen pair with G, C must be protonated at the N3 position. (b) The reverse Hoogsteen base triads.

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References

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Further Reading

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Frank‐Kamenetskii MD (1997) Unraveling DNA. Reading, MA: Perseus Books.

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Sinden RR (1994) DNA Structure and function. San Diego: Academic Press.

Soyfer VN and Potaman VV (1996) Triple Helical Nucleic Acids. New York: Springer.

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Frank‐Kamenetskii, Maxim D(Mar 2014) DNA Structure: Sequence Effects. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002976.pub2]