The major chromatin protein histone H1 binds preferentially to cis-platinum-damaged DNA.
Both cis-diamminedichloroplatinum(II) (cisplatin or cis-DDP) and trans-diamminedichloroplatinum(II) form covalent adducts with DNA. However, only the cis isomer is a potent anticancer agent. It has been postulated that the selective action of cis-DDP occurs through specific binding of nuclear proteins to cis-DDP-damaged DNA sites and that binding blocks DNA repair. We find that a very abundant nuclear protein, the linker histone H1, binds much more strongly to cis-platinated DNA than to trans-platinated or unmodified DNA. In competition experiments, H1 is shown to bind much more strongly than HMG1, which had been previously considered a major candidate for such binding in vivo.
Yaneva
J
J
Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Leuba
S H
SH
van Holde
K
K
Zlatanova
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D006609:High Mobility Group Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice
D000970:Antineoplastic Agents; D018736:DNA Adducts; D006609:High Mobility Group Proteins; D006657:Histones; D004247:DNA; D002945:Cisplatin