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Science 10 April 1992: Vol. 256. no. 5054, pp. 234 - 237 DOI: 10.1126/science.1566071
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Articles
Science, Vol 256, Issue 5054, 234-237
Copyright © 1992 by American Association for the Advancement of Science
Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin
PM Pil
and
SJ Lippard
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
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.
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