Solution Structure of a Duplex DNA with an Abasic Site in a dA Tract

Abstract

The presence of dA tracts in DNA can lead to stable curvature of the DNA, and this curvature can be important in gene regulation, DNA packaging, and other processes. Since damage to DNA may eliminate this stable curvature, the solution state structure of the duplex of d(CGCAAAAATGCG) paired with d(CGCATTDTTCCG), with D indicating an abasic site, has been determined. The undamaged DNA bends into the major groove both in solution and in the crystal state. The presence of the abasic site in the dA tract region induces changes in the DNA structure up to four base pairs away from the damaged site. The structure of the DNA is dependent on whether the abasic site is in the alpha or beta hemiacetal form. These consequences are quite different from the more localized effects that have been observed for "normal" DNAs containing abasic sites. Thus, there appears to be a strong sequence dependence of the structural effects of abasic sites just as there is for undamaged DNA. Furthermore, these results indicate that the presence of an abasic site can alter DNA bending and hence is likely to have significant long range effects on gene regulation and other properties that are dependent on the stable curvature of DNA.