Williams L D, Thivierge J, Goldberg I H
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Nucleic Acids Res. 1988 Dec 23;16(24):11607-15. doi: 10.1093/nar/16.24.11607.
DNA intercalators are found to recognize a DNA lesion as a high affinity receptor site. This lesion-specific binding is observed when one strand of a DNA double helix contains an extra, unpaired nucleotide. Our assay for binding controls for the effects of sequence with a series of oligodeoxynucleotide duplexes which are identical except for the location of the lesion, an extra cytidine. Scission of the series of oligodeoxynucleotides by the cuprous complex of ortho-phenanthroline (OP-Cu) indicates that OP-Cu binds at the lesion-specific stable intercalation site, suggesting that OP-Cu intercalates into DNA. The dispersion of OP-Cu scission sites over three residues is consistent with scission via a diffusible intermediate. The location of the scission sites, directly on the 3' side of the lesion, is consistent with minor groove binding in B DNA.
人们发现DNA嵌入剂将DNA损伤识别为高亲和力受体位点。当DNA双螺旋的一条链包含一个额外的未配对核苷酸时,就会观察到这种损伤特异性结合。我们通过一系列除损伤位置(一个额外的胞嘧啶)外完全相同的寡脱氧核苷酸双链体来检测结合对序列效应的控制。邻菲罗啉亚铜配合物(OP-Cu)对该系列寡脱氧核苷酸的切割表明,OP-Cu在损伤特异性稳定嵌入位点结合,这表明OP-Cu嵌入到DNA中。OP-Cu切割位点在三个残基上的分散与通过可扩散中间体进行的切割一致。切割位点直接位于损伤的3'侧,这与B型DNA中的小沟结合一致。