Histone H1 Interacts Preferentially with DNA Fragments Containing a Cisplatin- Induced 1,2-Intrastrand Cross-Link

Cisplatin [cis-diamminedichloroplatinum(II) or cisDDP], 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 intraand 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.