Wang K Y, Parker S A, Goljer I, Bolton P H
Chemistry Department, Wesleyan University, Middletown, Connecticut 06459, USA.
Biochemistry. 1997 Sep 30;36(39):11629-39. doi: 10.1021/bi971464l.
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.
DNA中dA序列的存在会导致DNA产生稳定的弯曲,这种弯曲在基因调控、DNA包装及其他过程中可能具有重要意义。由于DNA损伤可能消除这种稳定的弯曲,因此已确定了与d(CGCATTDTTCCG)配对的d(CGCAAAAATGCG)双链体的溶液状态结构,其中D表示无碱基位点。未受损的DNA在溶液和晶体状态下均向大沟弯曲。dA序列区域中无碱基位点的存在会在距损伤位点四个碱基对的范围内诱导DNA结构发生变化。DNA的结构取决于无碱基位点是处于α还是β半缩醛形式。这些结果与在含有无碱基位点的“正常”DNA中观察到的更局部的效应有很大不同。因此,无碱基位点的结构效应似乎与未受损DNA一样存在很强的序列依赖性。此外,这些结果表明无碱基位点的存在会改变DNA弯曲,因此可能对基因调控及其他依赖于DNA稳定弯曲的特性产生重大的长程影响。