Stability of DNA duplexes containing GG, CC, AA, and TT mismatches

We employed salt-dependent differential scanning calorimetric measurements to characterize the stability of six oligomeric DNA duplexes (5'-GCCGGAXTGCCGG-3'/5'-CCGGCAYTCCGGC-3') that contain in the central XY position the GC, AT, GG, CC, AA, or TT base pair. The heat-induced helix-to-coil transitions of all the duplexes are associated with positive changes in heat capacity, Delta C-p, ranging from 0.43 to 0.53 kcal/mol. Positive values of Delta C-p result in strong temperature dependences of changes in enthalpy, Delta H degrees, and entropy, Delta S degrees, accompanying duplex melting and cause melting free energies, Delta G degrees, to exhibit characteristically curved shapes. These observations suggest that Delta C-p needs to be carefully taken into account when the parameters of duplex stability are extrapolated to temperatures distant from the transition temperature, T-M. Comparison of the calorimetric and van't Hoff enthalpies revealed that none of the duplexes studied in this work exhibits two-state melting. Within the context of the central AXT/TYA triplet, the thermal and thermodynamic stabilities of the duplexes in question change in the following order: GC > AT > GG > AA approximate to TT > CC. Our estimates revealed that the thermodynamic impact of the GG, AA, and TT mismatches is confined within the central triplet. In contrast, the thermodynamic impact of the CC mismatch propagates into the adjacent helix domains and may involve 7-9 bp. We discuss implications of our results for understanding the origins of initial recognition of mismatched DNA sites by enzymes of the DNA repair machinery.