Structure and properties of hydroxyl radical modified nucleic acid components: tautomerism and miscoding properties of 5-hydroxycytosine

The SCF ab initio quantum chemistry calculations of the 5-hydroxycytosine (5-OH-C) tautomer and its pairs with standard nucleic acid bases were performed. In the vapour state the keto-imino isomer is most stable among all possible H-1 tautomers. However, in the presence of a solvent field the most preferred is the keto-amino isomer. Thus, there is significant influence of the environment polarity on the tautomers succession. Such a behaviour is related to discrepancies in the dipole moments between the two most stable tautomers of 5-OH-C. The keto-imino form is less polar and has a dipole moment one order less then the keto-amino structure. The pairing potential of 5-OH-C was estimated on the basis of SCF calculations for the two most favourable tautomers. Both structures are able to form stable dimers with guanine, cytosine and to a lesser extent with thymine and adenine. The first does not lead to miscoding abilities. However, the formation of all other dimers may be responsible for observed in vivo miscoding properties of this DNA lesion. A comparison of the stabilisation energies to AT pair led to the conclusion that the resulting stabilisation energy is higher for pairs with guanine and cytosine but slightly lower for pairs with thymine and adenine. The presence of one of these odd pairs in the DNA may be responsible for CG double right arrow GC and CG double right arrow AT transversion or CG double right arrow TA transitions. These facts are in good agreement with in vivo and in vitro experimental observations. In the light of our results the source of such mutations may be related not only to the miscoding potential of dominant tautomer, but also to other, less stable tautomers of 5-OH-C. (C) 1999 Elsevier Science B.V. All rights reserved.