Grimwade J E, Cullinan E B, Beerman T A
Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, NY 14263.
Biochim Biophys Acta. 1988 Jul 13;950(2):102-12. doi: 10.1016/0167-4781(88)90002-4.
Neocarzinostatin and auromomycin were shown to cleave simian virus 40 (SV40) DNA with preference for distinct regions of the viral genome. The positions cut by neocarzinostatin and auromomycin were similar, while micrococcal nuclease cleaved at positions other than those recognized by neocarzinostatin and auromomycin. Breaks were distributed throughout the viral genome and were not associated with any single type of genetic element. The limited number of locations in SV40 DNA that were preferentially cut by neocarzinostatin and auromomycin suggests that drug attack is directed by DNA structures other than the known trinucleotide sequence specificity of the drugs. Neocarzinostatin and auromomycin cut purified, cell-free, nuclear and intracellular chromosomal SV40 DNA at similar regions. The data indicate that there are regions in DNA that are hypersensitive to the drugs; the hypersensitivity may be determined by the microstructure of the DNA. The conformational change associated with the packing of the DNA into nucleosomes did not affect the microstructure of the sensitive region, nor did the shielding effect of nuclear proteins affect the drug's access to it. In addition, intracellular drug metabolism or other cellular factors did not alter the ability of drugs to interact at these sensitive regions.
