Coordinating the Two Protomer Active Sites of Human Topoisomerase IIα: Nicks as Topoisomerase II Poisons

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 II alpha 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.