DNA topoisomerase II (DNA-enzyme cleavage complex) (Top2cc)

DNA topoisomerase II is an essential nuclear enzyme that regulates DNA topology by generating transient double-strand breaks, allowing the passage of one DNA duplex through another. The DNA-enzyme cleavage complex (Top2cc) is a critical catalytic intermediate in this process, where the enzyme is covalently linked to the 5' phosphate ends of the DNA. This complex is the specific target of topoisomerase II poisons, a class of potent anticancer drugs including etoposide and doxorubicin. These agents act by stabilizing the cleavage complex and preventing the religation of the DNA strands, effectively converting the enzyme into a source of lethal, permanent double-strand breaks. The resulting genomic fragmentation triggers programmed cell death (apoptosis) in rapidly proliferating cancer cells. While these drugs are cornerstones of chemotherapy for various malignancies, their use is limited by significant safety concerns, most notably cardiotoxicity and the risk of therapy-related secondary leukemias.

Other names

Topoisomerase II-DNA covalent complexTop2-DNA adductCleavable complexTopoisomerase II-DNA crosslinkTop2cc

Stabilization of the covalent DNA-enzyme intermediate (cleavage complex) to prevent DNA religation, leading to permanent double-strand breaks and apoptosis.