Pommier Y, Mattern M R, Schwartz R E, Zwelling L A, Kohn K W
Biochemistry. 1984 Jun 19;23(13):2927-32. doi: 10.1021/bi00308a012.
Treatment of mammalian cells with DNA intercalating agents produces protein-associated DNA strand breaks. These breaks have been 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. Previously, we had proposed that intercalator-induced protein-associated DNA breaks 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.
用DNA嵌入剂处理哺乳动物细胞会产生与蛋白质相关的DNA链断裂。有人提出这些断裂代表了一种拓扑异构酶的作用，这种酶会改变DNA的连环数。通过对核仁沉降进行溴化乙锭滴定，研究了用嵌入剂4'-（9-吖啶基氨基）甲磺酰基间氨基苯甲醚（m-AMSA）处理的细胞中DNA连环数的变化。发现m-AMSA处理会导致DNA连环数增加。此前，我们曾提出嵌入剂诱导的与蛋白质相关的DNA断裂起到减少因嵌入剂诱导的DNA扭曲减少而产生的DNA扭转应变的作用。在这样一个模型中，预计连环数会减少。m-AMSA处理后DNA连环数增加这一发现表明，嵌入剂可能会阻断通常会减少连环数的酶。这种酶将具有类似DNA促旋酶的特性。与此可能性一致的是，一种DNA促旋酶抑制剂新生霉素，抑制了正常连环数的恢复，并在较小程度上抑制了去除嵌入剂后与蛋白质相关的链断裂的逆转。
