Platinum-DNA crosslinking: platinum antitumor drug interactions with native lambda bacteriophage DNA studied using a restriction endonuclease

Abstract

These studies demonstrate the novel principle that the restriction endonuclease Bam HI appears to maintain specific phosphodiester bond cutting even in the presence of platinum bound to the DNA substrate recognition sequence. Separation of the cleaved DNA into classical restriction endonuclease fragments is blocked by platinum intrastrand or interstrand crosslinks. Recovery of separate fragments is achieved by dialysis against KCN after the enzyme is inactivated. The present study is consistent with the occurrence of GpG intrastrand crosslinking by platinum bound to N(7) sites of the guanines on either side of the cleavage site, and our previous work indicating a preference for binding to GpG sequences. This study also directs attention toward additional crosslink sites in the Bam HI recognition sequence 5′-GGATCC-3′.