Differences between sites of binding to DNA and strand cleavage for complexes of bleomycin with iron of cobalt

✍ Scribed by Michael J. McLean; Ahsana Dar; Michael J. Waring

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 861 KB
• Volume: 1
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/jmr.300010407

✦ Synopsis

The sequence specificity of bleomycin A5 and of its light-activated cobalt complex were compared by examining the relative cleavage of each strand of two DNA fragments by either species. Significant differences between the two metallobleomycins were observed. The iron-bleomycin (Fe-BLM) complex cleaved the DNA molecules preferentially at dinucleotides G,T and G,C, whereas the light-activated cobalt-bleomycin complex (Co-BLM) showed a preference for cutting a t the dinucleotide G,A in addition to cleavage at every G,T dinucleotide. Further, new sites of preferential cleavage were noted for Co-BLM in regions of the DNA where enhanced reaction with DNAaseI can be observed in the presence of the antibiotic. No differences in the cutting behaviour of the Fe-BLM were evident upon irradiation of the reaction mixture. A reduction in the relative efficiency of cutting at G,C sequences by Co-BLM is responsible for the previously observed diminution of double-strand breaks under conditions of photoactivated cleavage. The results are discussed in terms of the likely production of highly reactive, diffusible cutting elements in the light activated reaction which cause cleavage of the DNA in regions where the antibiotic is not bound.