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.

Linker histones do not interact with DNA containing a single interstrand cross-link created by cisplatin.

During our earlier investigations we have observed a prominent preference of the linker histone H1 for binding to a cis-platinated DNA (a synthetic fragment with global type of platination in respect to targets for cisplatin) comparing with unmodified and trans-Pt-modified DNA. In the present work we report our recent experimental results on the binding of the linker histones H1 and H5 to a cisplatin-modified synthetic DNA fragment containing a single nucleotide target d(GC/CG) for inter-platination. Surprisingly, no preferential binding of linker histones to cis-inter-platinated DNA was observed by means of the electromobility-shift assay.