Effects of 9-aminoacridine on bacteriophage T4 deoxyribonucleic acid synthesis

When 9-aminoacridine is included in the culture medium of Escherichia coli infected with bacteriophage T4, various effects upon the fate of radioactively labeled intracellular phage DNA as examined by various sedimentation studies are observed. The rates of production of mature phage particles and a replicative intermediate form of DNA are much more severely affected than the gross rate of DNA synthesis. 9-Aminoacridine disturbs the normal function of the replicative process to yield large amounts of newly synthesized, small T4 DNA fragments and appears to block release of parental DNA from the replicative complex. The presence of a 9-aminoacridine resistance marker in the infecting phage relieves the inhibition both of the final packaging step, and in part, the malfunctioning of the earlier replicative steps. DNA synthesis is necessary for production of viable phage after 9-aminoacridine (at optimum concentration) is removed from the culture medium at 20 minutes after infection. The size, of the small DNA fragments produced when 9-aminoacridine is present is dependent upon the concentration of the drug and as development progresses, the later fragments more nearly approach the size of phage DNA. Part of this DNA appears to be utilized in subsequent replication when 9-aminoacridine is removed from the culture medium. The effect of 9-aminoacridine upon phage DNA packaging is distinct from that upon the production of normal replicating DNA within the cell.