Fluctuational opening of the double helix as revealed by theoretical and experimental study of DNA interaction with formaldehyde

Alexander V. Lukashin, Alexander V. Vologodskii, Maxim D. Frank-Kamenetskii, Yuri L Lyubchenko

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Abstract

It follows from the theory of helix-coil transition that local opening of the double helix due to thermal fluctuations must take place at temperatures well below the melting range. Provided that formaldehyde can not react with hydrogen-bonded bases and can react only with the exposed ones, such fluctuational opening of base-pairs may be probed by formaldehyde. To test the adequacy of the theory for describing the fluctuational opening of the double helix, the process of DNA interaction with formaldehyde has been simulated by the Monte Carlo method with the aid of a computer. On the basis of kinetic constants for the forward and reverse reactions of formaldehyde with all four nucleotides measured by McGhee & von Hippel (1975a,b), the kinetic curves of DNA unwinding by formaldehyde have been calculated theoretically without the use of any adjustable parameter. The calculations have demonstrated that the highly reversible but very fast reaction of formaldehyde with the imino group of thymine plays a very important role in the process of DNA unwinding by formaldehyde have been compared with experimental data obtained for bacteriophage T7 DNA for different values of pH, temperature and concentration of formaldehyde. This comparison leads to the conclusion that the theory offers a correct general description of fluctuational opening of the double helix. The main characteristics of this process calculated by the theory are as follows. At room temperatures only individual base-pairs are opened and the mean distance between adjacent unpaired bases is as great as 2×105 base-pairs. Each A·T pair is shown to be opened with frequency about 102 s-1 and each G·C pair with a frequency about 10 s-1. At elevated temperatures, in the DNA premelting region, the probability of fluctuational opening, as well as the average number of base-pairs in an opened region, increases considerably. A possible role of the results obtained from an analysis of the processes of DNA function in the cell is discussed.

Original languageEnglish (US)
Pages (from-to)665-682
Number of pages18
JournalJournal of Molecular Biology
Volume108
Issue number4
DOIs
StatePublished - Dec 25 1976

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Formaldehyde
Theoretical Models
DNA
Base Pairing
Temperature
Bacteriophage T7
Monte Carlo Method
Thymine
Freezing
Hydrogen
Nucleotides
Hot Temperature

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Fluctuational opening of the double helix as revealed by theoretical and experimental study of DNA interaction with formaldehyde. / Lukashin, Alexander V.; Vologodskii, Alexander V.; Frank-Kamenetskii, Maxim D.; Lyubchenko, Yuri L.

In: Journal of Molecular Biology, Vol. 108, No. 4, 25.12.1976, p. 665-682.

Research output: Contribution to journalArticle

Lukashin, Alexander V. ; Vologodskii, Alexander V. ; Frank-Kamenetskii, Maxim D. ; Lyubchenko, Yuri L. / Fluctuational opening of the double helix as revealed by theoretical and experimental study of DNA interaction with formaldehyde. In: Journal of Molecular Biology. 1976 ; Vol. 108, No. 4. pp. 665-682.
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abstract = "It follows from the theory of helix-coil transition that local opening of the double helix due to thermal fluctuations must take place at temperatures well below the melting range. Provided that formaldehyde can not react with hydrogen-bonded bases and can react only with the exposed ones, such fluctuational opening of base-pairs may be probed by formaldehyde. To test the adequacy of the theory for describing the fluctuational opening of the double helix, the process of DNA interaction with formaldehyde has been simulated by the Monte Carlo method with the aid of a computer. On the basis of kinetic constants for the forward and reverse reactions of formaldehyde with all four nucleotides measured by McGhee & von Hippel (1975a,b), the kinetic curves of DNA unwinding by formaldehyde have been calculated theoretically without the use of any adjustable parameter. The calculations have demonstrated that the highly reversible but very fast reaction of formaldehyde with the imino group of thymine plays a very important role in the process of DNA unwinding by formaldehyde have been compared with experimental data obtained for bacteriophage T7 DNA for different values of pH, temperature and concentration of formaldehyde. This comparison leads to the conclusion that the theory offers a correct general description of fluctuational opening of the double helix. The main characteristics of this process calculated by the theory are as follows. At room temperatures only individual base-pairs are opened and the mean distance between adjacent unpaired bases is as great as 2×105 base-pairs. Each A·T pair is shown to be opened with frequency about 102 s-1 and each G·C pair with a frequency about 10 s-1. At elevated temperatures, in the DNA premelting region, the probability of fluctuational opening, as well as the average number of base-pairs in an opened region, increases considerably. A possible role of the results obtained from an analysis of the processes of DNA function in the cell is discussed.",
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