Deweese Joseph E, Osheroff Neil
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Biochemistry. 2009 Feb 24;48(7):1439-41. doi: 10.1021/bi8021679.
Topoisomerase II modulates DNA topology by generating double-stranded breaks in DNA. Results of the current study indicate that the presence of a nick at one scissile bond dramatically increases the rate of cleavage by human topoisomerase IIalpha at the scissile bond on the opposite strand. We propose that this enhanced activity at the second strand coordinates the two protomer subunits of topoisomerase II and allows the enzyme to create double-stranded breaks. Finally, the presence of a nick on one strand induces cleavage on the opposite strand. Thus, nicks are topoisomerase II poisons that generate novel sites of DNA cleavage.
拓扑异构酶II通过在DNA中产生双链断裂来调节DNA拓扑结构。当前研究结果表明，在一个可切割键处存在一个切口会显著提高人类拓扑异构酶IIα在相反链上可切割键处的切割速率。我们提出，第二条链上这种增强的活性协调了拓扑异构酶II的两个原体亚基，并使该酶能够产生双链断裂。最后，一条链上存在切口会诱导相反链上的切割。因此，切口是产生新的DNA切割位点的拓扑异构酶II毒药。
