Recognition of DNA interstrand cross-links of cis-diamminedichloroplatinum(II) and its trans isomer by DNA-binding proteins
Language English Country United States Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
7547982
DOI
10.1021/bi00038a035
Knihovny.cz E-resources
- MeSH
- DNA Adducts metabolism MeSH
- Cisplatin metabolism MeSH
- DNA Footprinting MeSH
- DNA-Binding Proteins metabolism MeSH
- Endodeoxyribonucleases metabolism MeSH
- Binding, Competitive MeSH
- Nucleic Acid Conformation MeSH
- Molecular Sequence Data MeSH
- DNA Damage MeSH
- High Mobility Group Proteins metabolism MeSH
- Antineoplastic Agents metabolism MeSH
- Cross-Linking Reagents metabolism MeSH
- Base Sequence MeSH
- Substrate Specificity MeSH
- Protein Binding MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- DNA Adducts MeSH
- Cisplatin MeSH
- DNA-Binding Proteins MeSH
- endodeoxyribonuclease VII MeSH Browser
- Endodeoxyribonucleases MeSH
- High Mobility Group Proteins MeSH
- Antineoplastic Agents MeSH
- Cross-Linking Reagents MeSH
- transplatin MeSH Browser
Recognition and processing by cellular proteins of DNA modified by platinum complexes have been suggested to be relevant to the mechanism of their antitumor activity. Platinum complexes form on DNA various mono- and bifunctional adducts. It has already been described by other authors that intrastrand cross-links formed on DNA by antitumor cis-diamminedichloroplatinum(II) (cisplatin) between neighboring purine residues are recognized by several DNA-binding proteins. In contrast, these proteins do not recognize the intrastrand cross-links formed on DNA by cisplatin or its clinically ineffective trans isomer (transplatin) between nonadjacent base residues. An eventuality heretofore not addressed is that DNA interstrand cross-links (ICLs) of platinum compounds may be recognized by and bound to DNA-binding proteins. DNA probes of 110 base pairs (bp) were constructed containing five equally spaced ICLs of cisplatin or transplatin. These ICLs were formed at specific sites at which these adducts are preferentially formed in natural DNA. Gel electrophoresis mobility shift and competition assays with these probes were used to investigate the specific recognition and binding of the calf thymus HMG1 protein to the DNA ICLs of both platinum isomers. The ICL of antitumor cisplatin was recognized by and bound to the HMG1 protein with a similar affinity as the 1,2-intrastrand d(GpG) cross-link of this drug. The protein binding to the ICL is selective for the DNA modification by cisplatin, but not by chemotherapeutically inactive transplatin.(ABSTRACT TRUNCATED AT 250 WORDS)
References provided by Crossref.org
