Grokhovsky S L
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Mol Biol (Mosk). 2018 Jul-Aug;52(4):705-717. doi: 10.1134/S0026898418040067.
Ligand binding influences the dynamics of the DNA helix in both the binding site and adjacent regions. This, in particular, is reflected in the changing pattern of cleavage of complexes under the action of ultrasound. The specificity of ultrasound-induced cleavage of the DNA sugar-phosphate backbone was studied in actinomycin D (AMD) complexes with double-stranded DNA restriction fragments. After antibiotic binding, the cleavage intensity of phosphodiester bonds between bases was shown to decrease at the chromophore intercalation site and to increase in adjacent positions. The character of cleavage depended on the sequences flanking the binding site and the presence of other AMD molecules bound in the close vicinity. A comparison of ultrasonic and DNase I cleavage patterns of AMD-DNA complexes provided more detail on the local conformation and dynamics of the DNA double helix in both binding site and adjacent regions. The results pave the way for developing a novel approach to studies of the nucleotide sequence dependence of DNA conformational dynamics and new techniques to identify functional genome regions.
配体结合会影响结合位点及相邻区域中DNA螺旋的动力学。这一点尤其体现在超声作用下复合物切割模式的变化上。在放线菌素D（AMD）与双链DNA限制性片段形成的复合物中，研究了超声诱导的DNA糖磷酸主链切割的特异性。抗生素结合后，发色团嵌入位点处碱基间磷酸二酯键的切割强度降低，而相邻位置的切割强度增加。切割特征取决于结合位点两侧的序列以及紧邻处结合的其他AMD分子的存在。对AMD-DNA复合物的超声切割模式和DNase I切割模式进行比较，能更详细地了解结合位点及相邻区域中DNA双螺旋的局部构象和动力学。这些结果为开发一种研究DNA构象动力学核苷酸序列依赖性的新方法以及鉴定功能基因组区域的新技术铺平了道路。
