| Abstract
| - The abasic site in DNA may arise spontaneously, as a result ofnucleotide base damage, or asan intermediate in glycosylase-mediated DNA-repair pathways. It isthe most common damage found inDNA. We have examined the consequences of this lesion and itssequence context on DNA duplexstructure, as well as the thermal and thermodynamic stability of theduplex, including the energetic originsof that stability. To this end, we incorporated a tetrahydrofuranabasic site analogue into a family of13-mer DNA duplexes, wherein the base opposite the lesion (A, C, G, orT) and the base pairs neighboringthe lesion (C·G or G·C) were systematically varied andcharacterized by a combination of spectroscopicand calorimetric techniques. The resulting data allowed us toreach the following conclusions: (i) thepresence of the lesion in all sequence contexts studied does not alterthe global B-form conformationcharacteristic of the parent undamaged duplex; (ii) the presence of thelesion induces a significant enthalpicdestabilization of the duplex, with the magnitude of this effect beingdependent on the sequence context;(iii) the thermodynamic impact of the lesion is dominated by theidentity of the neighboring base pairs,with the cross strand partner base exerting only a secondarythermodynamic effect on duplex properties.In the aggregate, our data reveal that even in the absence oflesion-induced alterations in global structure,the abasic lesion can significantly alter the thermodynamic propertiesof the host duplex, with the magntiudeof this impact being strongly dependent on sequencecontext.
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