title: Selective binding of actinomycin D and distamycin A to DNA.
abstract: The exact sites at which a number of drugs inhibit the nick translation of DNA by E.coli DNA polymerase-I have been pinpointed. In order to do this, a method has been developed for sequencing double-stranded plasmid DNA from the site of a specifically induced nick. The initial experiments have concentrated on analysis of drug inhibition of nick translation in a 200 nucleotide region near the Eco Rl origin of pBR313. Many drugs were found to inhibit nick translation in a highly sequence specific manner. For actinomycin D, significant inhibition occurred at just four sites in the nucleotide sequence under test and only one sequence (pGpCpGpCpGpGp) gave really strong inhibition. Distamycin A gave a different pattern of inhibition with particularly strong stops in just two of the many A-T rich regions in the DNA. Experiments with caffeine suggest that factors in addition to primary sequence are important in determining where major inhibition occurs.
mesh_terms: D000260:Adenoviruses, Human; D001483:Base Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors*; D004262:DNA Restriction Enzymes; D004279:DNA, Viral; D003609:Dactinomycin / Q000494:pharmacology*; D004214:Distamycins / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D019384:Nucleic Acid Synthesis Inhibitors; D010957:Plasmids; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D004279:DNA, Viral; D004214:Distamycins; D019384:Nucleic Acid Synthesis Inhibitors; D011758:Pyrroles; D003609:Dactinomycin; C030000:stallimycin; D004256:DNA Polymerase I; D004262:DNA Restriction Enzymes