DNA unwinding produced by site-specific intrastrand cross-links of the antitumor drug cis-diammine-dichloroplatinum(II)

The DNA unwinding produced by specific adducts of the antitumor drug cis-diammine-dichloroplatinum(II) has been quantitatively determined. Synthetic DNA duplex oligonucleotides of varying lengths with two base pair cohesive ends were synthesized and characterized that contained site-specific intrastrand N7-purine/N7-purine cross-links. On the basis of an analysis of the present and other published studies of site-specifically modified DNA, we propose that local duplex unwinding is a major determinant in the recognition of DNA damage by the Escherichia coli (A)BC excinuclease.