cis-Diamminedichloroplatinum(II) selectively cross-links high mobility group proteins 1 and 2 to DNA in micrococcal nuclease accessible regions of chromatin.
The reaction of cis-diamminedichloroplatinum(II) with chicken erythrocyte nuclei produces covalent cross-linking of HMG proteins 1, 2 and E to DNA, in addition to cross-links amongst LMG proteins. This is supported by and consistent with the observations that all cross-links are chemically reversed by NaCN treatment, while only the cross-links involving the HMG proteins 1,2 and E are eliminated after a limited digestion with micrococcal nuclease. Having identified the subset of proteins selectively cross-linked to DNA by the bifunctional cis-(NH3)2PtCl2, a tentative model is proposed for the interactions between DNA and HMG proteins 1 and 2 in bulk chromatin. In addition, possible modes of action for this anti-neoplastic drug are suggested in light of these findings.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism*; D002945:Cisplatin / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004247:DNA / Q000097:blood*; D004912:Erythrocytes / Q000648:ultrastructure*; D006609:High Mobility Group Proteins / Q000097:blood*; D008836:Micrococcal Nuclease / Q000378:metabolism*; D012966:Sodium Cyanide / Q000494:pharmacology
D002843:Chromatin; D003432:Cross-Linking Reagents; D006609:High Mobility Group Proteins; D004247:DNA; D008836:Micrococcal Nuclease; D012966:Sodium Cyanide; D002945:Cisplatin