SPECIFIC BINDING OF CHROMOSOMAL PROTEIN-HMG1 TO DNA DAMAGED BY THE ANTICANCER DRUG CISPLATIN
SPECIFIC BINDING OF CHROMOSOMAL PROTEIN-HMG1 TO DNA DAMAGED BY THE ANTICANCER DRUG CISPLATIN
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DOI：
10.1126/science.1566071
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发表时间：
1992-04-10
期刊：
影响因子：
56.9
通讯作者：
LIPPARD, SJ
中科院分区：
文献类型：
--
作者：
PIL, PM;LIPPARD, SJ
抗癌化合物顺二氨二氯铂（II）（顺铂）的作用机制涉及与DNA的共价结合。为了理解这种DNA损伤的肿瘤特异性细胞毒性，研究了这些损伤与细胞蛋白的相互作用。一种这样的蛋白质已被鉴定为高迁移率族蛋白HMG 1。重组大鼠HMG 1与含有顺铂d（GpG）或d（ApG）链内交联的DNA特异性结合（解离常数为3.7 +/- 2.0 x 10（-7）摩尔），这些交联以特异性方式解开和弯曲DNA，但不与经治疗上无活性的铂类似物修饰的DNA结合。这些结果表明HMG 1可能与改变的DNA结构结合，并可能有助于设计新的抗肿瘤药物。
The mechanism of action of the anticancer compound cis-diamminedichloroplatinum(II) (cisplatin) involves covalent binding to DNA. In an effort to understand the tumor-specific cytotoxicity of such DNA damage, the interactions of these lesions with cellular proteins have been studied. One such protein has been identified as the high-mobility group protein HMG1. Recombinant rat HMG1 binds specifically (dissociation constant 3.7 +/- 2.0 x 10(-7) molar) to DNA containing cisplatin d(GpG) or d(ApG) intrastrand cross-links, which unwind and bend DNA in a specific manner, but not to DNA modified by therapeutically inactive platinum analogs. These results suggest how HMG1 might bind to altered DNA structures and may be helpful in designing new antitumor drugs.