SPECIFIC BINDING OF CHROMOSOMAL PROTEIN-HMG1 TO DNA DAMAGED BY THE ANTICANCER DRUG CISPLATIN

被引：527

作者：

PIL, PM ^{[1
]}

LIPPARD, SJ ^{[1
]}

机构：

[1] MIT,DEPT CHEM,CAMBRIDGE,MA 02139

来源：

SCIENCE | 1992年 / 256卷 / 5054期

关键词：

D O I：

10.1126/science.1566071

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：234 / 237

页数：4

共 29 条

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