Action of bleomycin on structural mimics of intermediates in DNA double-strand cleavage.
Bleomycin-induced cleavage was examined in several nicked, gapped, or intact duplex DNA substrates, including a structure designed to mimic a proposed singly nicked intermediate in double-strand cleavage. This nicked structure appeared to correctly target the second cleavage event in the complementary strand, resulting in a blunt-ended double-strand break, similar to that induced directly by bleomycin alone in an intact duplex of the same sequence. A one-base-gapped structure was markedly less efficient in correctly targeting bleomycin attack in the complementary strand. The results are consistent with a model of bleomycin-induced double-strand cleavage in which the nick formed by the initial bleomycin attack serves to target secondary attack to a specific position in the complementary strand, resulting in a double-strand break with a defined geometry.
Charles
K
K
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Povirk
L F
LF
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D006151:Guanosine / Q000737:chemistry; D007288:Inosine / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D006151:Guanosine; D007288:Inosine; D004247:DNA; D010100:Oxygen