Nalidixic acid prevents the induction of yeast cytoplasmic respiration‐deficient mutants by intercalating drugs

The mechanism of DNA replication in viva is not yet clarified [l] . In view of complex organization of DNA in nuclei of eukaryotic organisms, the replication mechanism is mostly being studied in simpler systems, in bacteria and in the organelles of eukaryotic cells, i.e. chloroplasts and mitochondria. In yeast, disturbance in replication of mitochrondrial DNA (mt-DNA) results in the formation of cytoplasmic respiration-deficient mutants [2, 31 . The mutants have proven to be invaluable tools in the study of cytoplasmic heredity and of the structure and function of mitochondria. More recently, the potentialities for the elucidation of the mechanism of DNA replication have been implicated [4-71. This paper shows that nalidixic acid, an inhibitor of DNA replication in bacteria [8,9], prevents the induction of the respiration-deficient @-) mutants by ethidium or acriflavin. External circumstances have caused a delay in the publication of these results. In the meantime, Hollenberg and Borst [lo] reported that nalidixic acid at a concentration of 500 /~/ml inhibited the induction of pmutants by ethidium and concluded that mt-DNA replication may be required for mutant induction. In this paper, a different interpretation, assuming interference of nalidixic acid in nicking-closing cycles of mt-DNA triggered by ethidium, is proposed and additional data are presented to support the interpretation.