THE MAJOR CHROMATIN PROTEIN HISTONE H1 BINDS PREFERENTIALLY TO CIS-PLATINUM-DAMAGED DNA

Both cis-diamminedichloroplatinum (II) (cisplatin or cis-DDP) and tran s-diamminedichloroplatinum (II) form covalent adducts with DNA. Howeve r, only the cis isomer is a potent anticancer agent. It has been postu lated that the selective action of cis-DDP occurs through specific bin ding 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 previou sly considered a major candidate for such binding in vivo.