Histone H1 interacts preferentially with DNA fragments containing a cisplatin-induced 1,2-intrastrand cross-link.

Cisplatin [cis-diamminedichloroplatinum(II) or cis-DDP], but not its stereoisomer transplatin, is suggested to be among the most powerful anticancer agents. It is believed that its therapeutic activity results from its interaction with DNA forming intra- and interstrand crosslinks. During our earlier investigations, we have observed a prominent preference of the linker histone H1 for binding to cis-platinated DNA (containing several different cross-links along the DNA fragment) compared with unmodified or transplatin-modified DNA. This report presents our recent experimental data obtained by band-shift analysis on the binding of H1 to a cisplatin-modified synthetic 34 bp DNA fragment containing a single target d(GG/CC) for 1,2 cis-intra-platination. Results obtained with another nuclear protein with similar DNA-binding properties, HMGB1, are also presented. The experimental data throw light on the precise preference of histone H1 for binding to different types of cisplatin-created cross-links in DNA.