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Differences between sites of binding to DNA and strand cleavage for complexes of bleomycin with iron of cobalt
Author(s) -
McLean Michael J.,
Dar Ahsana,
Waring Michael J.
Publication year - 1989
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.300010407
Subject(s) - cleavage (geology) , dna , cobalt , chemistry , bleomycin , dna damage , molecule , stereochemistry , biochemistry , biology , genetics , organic chemistry , paleontology , chemotherapy , fracture (geology)
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 p T and G p C, whereas the light‐activated cobalt‐bleomycin complex (Co–BLM) showed a preference for cutting at the dinucleotide G p A in addition to cleavage at every G p 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 p C sequences by Co–BLM is responsible for the previously observed diminution of double‐strand breaks under condition 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.