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Effects of acridines on DNA synthesis in vitro

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Summary

Acridines are known to induce with a very high efficiency the cytoplasmic “petite” mutation in yeast. Since in “petite” mutants the base composition of mitochondrial DNA is altered, these dyes should interfere in the replication of mitochondrial DNA. To approach this problem a detailed knowledge of the effect of acridines on DNA synthesis is necessary.

The inhibitory effect of two acridines and of the related dye methylene blue on Escherichia coli DNA polymerase has been studied under different assay conditions. Several aspects of this inhibitory effect have been investigated including the extent of inhibition in the presence of several primers, the effect of acridines on the unprimed synthesis and on the addition of single nucleoside triphosphates to DNA 3′-OH terminals, the effect of preincubation of DNA and of DNA polymerase with acridines and the base composition of DNA synthesized in the presence of the dyes.

The extent of inhibition has not been found to be dependent on the base composition of the primer except in the case of primers very rich in A+T, while a strong effect on the unprimed synthesis is due to a substantial increase of the lag period. The A/C ratio in the product synthesized under strongly inhibitory conditions is shifted with respect to that of the primer.

The results seem to indicate the preferential replication, in the presence of acridines, of A+T rich regions of DNA.

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Communicated by G. Magni

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Arcà, M., Caneva, R., Frontali, L. et al. Effects of acridines on DNA synthesis in vitro . Molec. Gen. Genet. 114, 290–296 (1972). https://doi.org/10.1007/BF00267497

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