DNA topoisomerase II alpha-DNA complex (TOP2A-DNA complex)

DNA topoisomerase II alpha (TOP2A) is an ATP-dependent nuclear enzyme that manages DNA topology by making transient double-strand breaks, enabling the passage of another DNA helix through the gap[1][2][5][8][10]. This mechanism is crucial for the relaxation of supercoiled DNA, chromosome segregation, and decatenation after replication[7][8]. TOP2A is essential for cell proliferation and highly expressed in dividing cells, making it a critical cancer target[6][7][8]. Many chemotherapeutic agents act by stabilizing the transient covalent complex formed between TOP2A and DNA, causing irreversible DNA damage and apoptosis[3][9][10]. The drug-stabilized TOP2A-DNA cleavage complex interrupts DNA religation, resulting in cell death but also contributing to genotoxic side effects[6][10]. Selective inhibition of TOP2A versus TOP2B is an ongoing therapeutic challenge to avoid adverse events like secondary leukemias[6][9]. The full-length structure of the TOP2A-DNA complex has illuminated the enzyme’s domain organization and revealed targets for selective drug design[2][4][5][10].

Other names

DNA topoisomerase II alphaTopoisomerase II alphaTOP2ATopo IIαType IIA topoisomerase

Topoisomerase II poisons: stabilize the covalent TOP2A-DNA cleavage complex, thereby preventing DNA religation and causing double-strand DNA breaks, which trigger cell death\nCatalytic inhibitors: target the enzyme’s ability to manipulate DNA topology but do not induce DNA breaks