Specificity of deoxyribonucleic acid cleavage by bleomycin, phleomycin, and tallysomycin.
The sites of cleavage of DNA by bleomycin A2, bleomycin B2, phleomycin, tallysomycin A, and Blenoxane (Bristol-Meyers) in reactions containing equimolar Fe2+ and atmospheric oxygen were analyzed by gel electrophoresis of 32P end labeled DNA fragments. Bleomycin A2 and bleomycin B2 reactions cleaved DNA at all sites with a frequency equal to that of Blenoxane. At high concentrations of bleomycin the site specificity of cleavage was unchanged. Bleomycin cleavage sites and phleomycin cleavage sites are a subset of sites cleaved in reactions containing tallysomycin A. The nature of 5' and 3' termini induced by bleomycin cleavage was investigated. Electrophoresis of bleomycin-induced fragments after alkaline phosphatase or polynucleotide kinase treatment indicated that 5' termini are phosphoryl groups but 3' termini are not simple phosphoryl groups. Analysis of bleomycin cleavage of single-stranded DNA substrate showed that cleavage occurs only in regions of potentially double-stranded looped-back sequences. Possible mechanisms for determination of bleomycin cleavage sequence specificity are discussed.
D001483:Base Sequence; D001761:Bleomycin / Q000494:pharmacology* / Q000031:analogs & derivatives; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D004277:DNA, Single-Stranded; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005296:Ferrous Compounds / Q000494:pharmacology; D010692:Phleomycins / Q000494:pharmacology*
D004277:DNA, Single-Stranded; D005296:Ferrous Compounds; D010692:Phleomycins; D001761:Bleomycin; D004247:DNA; C016126:talisomycin