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Biophys J, December 1999, p. 3242-3251, Vol. 77, No. 6

Heat Capacity Effects on the Melting of DNA. 1. General Aspects

Ioulia Rouzina and Victor A. Bloomfielddagger

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, St. Paul, Minnesota 55108 USA

In this paper we analyze published data on Delta H and Delta S values for the DNA melting transition under various conditions. We show that there is a significant heat capacity increase Delta Cp associated with DNA melting, in the range of 40-100 cal/mol K per base pair. This is larger than the transition entropy per base pair, Delta S0 approx  25 cal/mol K. The ratio of Delta Cp/Delta S0 determines the importance of heat capacity effects on melting. For DNA this ratio is 2-4, larger than for many proteins. We discuss how Delta Cp values can be extracted from experimental data on the dependence of Delta H and Delta S on the melting temperature Tm. We consider studies of DNA melting as a function of ionic strength and show that while polyelectrolyte theory provides a good description of the dependence of Tm on salt, electrostatics alone cannot explain the accompanying strong variation of Delta H and Delta S. While Tm is only weakly affected by Delta Cp, its dependence on one parameter (e.g., salt) as a function of another (e.g., DNA composition) is determined by Delta Cp. We show how this accounts for the stronger stabilization of AT relative to GC base pairs with increasing ionic strength. We analyze the source of discrepancies in Delta H as determined by calorimetry and van't Hoff analysis and discuss ways of analyzing data that yield valid van't Hoff Delta H. Finally, we define a standard state for DNA melting, the temperature at which thermal contributions to Delta H and Delta S vanish, by analyzing experimental data over a broad range of stabilities.

Biophys J, December 1999, p. 3242-3251, Vol. 77, No. 6
© 1999 by the Biophysical Society   0006-3495/99/12/3242/10  $2.00



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