Coordinating the two protomer active sites of human topoisomerase IIalpha: 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 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.
Deweese
Joseph E
JE
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Osheroff
Neil
N
D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D059005:Topoisomerase II Inhibitors
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II