Changes in deoxyribonucleic acid linking number due to treatment of mammalian cells with the intercalating agent 4'-(9-acridinylamino)methanesulfon-m-anisidide

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Abstract
Treatment of mammalian cells with DNA intercalating agents produces protein-associated DNA strand breaks. These breaks were proposed to represent the action of a topoisomerase, which would alter the DNA linking number. Changes in DNA linking number, in cells treated with the intercalating agent 4''-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), were studied by ethidium titration of nucleoid sedimentation. m-AMSA treatment was found to produce an increase in DNA linking number. Intercalator-induced, protein-associated DNA breaks may act to reduce DNA torsional strain that results from the intercalator-induced decrease in DNA twist. In such a model, linking number would be expected to decrease. The finding that the DNA linking number increased following m-AMSA treatment suggests that intercalators may block enzymes that normally decrease linking number. Such enzymes would have DNA gyrase-like properties. Consistent with this possibility, a DNA gyrase inhibitor, novobiocin, inhibited the restoration of normal linking number and, to a lesser degree, the reversal of protein-associated strand breaks after removal of intercalator.