Gao Q, Williams L D, Egli M, Rabinovich D, Chen S L, Quigley G J, Rich A
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2422-6. doi: 10.1073/pnas.88.6.2422.
Ditercalinium is a synthetic anticancer drug that binds to DNA by bis-intercalation and activates DNA repair processes. In prokaryotes, noncovalent DNA-ditercalinium complexes are incorrectly recognized by the uvrABC repair system as covalent lesions on DNA. In eukaryotes, mitochondrial DNA is degraded by excess and futile DNA repair. Using x-ray crystallography, we have determined, to 1.7 A resolution, the three-dimensional structure of a complex of ditercalinium bound to the double-stranded DNA fragment [d(CGCG)]2. The DNA in the complex with ditercalinium is kinked (by 15 degrees) and severely unwound (by 36 degrees) with exceptionally wide major and minor grooves. Recognition of the DNA-ditercalinium complex by uvrABC in prokaryotes, and by mitochondrial DNA repair systems in eukaryotes, might be related to drug-induced distortion of the DNA helix.
地特卡林是一种合成抗癌药物，它通过双插入作用与DNA结合并激活DNA修复过程。在原核生物中，uvrABC修复系统会将非共价的DNA-地特卡林复合物错误地识别为DNA上的共价损伤。在真核生物中，线粒体DNA会因过量且无效的DNA修复而降解。利用X射线晶体学，我们已将地特卡林与双链DNA片段[d(CGCG)]2形成的复合物的三维结构解析到1.7埃的分辨率。与地特卡林形成复合物的DNA发生了扭结（15度）并严重解旋（36度），其大沟和小沟异常宽阔。原核生物中的uvrABC以及真核生物中的线粒体DNA修复系统对DNA-地特卡林复合物的识别，可能与药物诱导的DNA螺旋扭曲有关。
