DNA topoisomerase IIβ–DNA cleavage complex (TOP2B-DNA CC)

The DNA topoisomerase IIβ–DNA cleavage complex is a transient intermediate formed during the catalytic cycle of the TOP2B enzyme, where the protein is covalently linked to a double-stranded DNA break. Unlike the alpha isoform (TOP2A), which is primarily associated with DNA replication in proliferating cells, TOP2B is expressed in both dividing and post-mitotic cells, playing a critical role in transcription-induced DNA tension relief and regulated gene expression. This complex is the primary pharmacological target of 'topoisomerase poisons' such as anthracyclines and etoposide, which trap the enzyme in its cleaved state. While this mechanism is effective in inducing apoptosis in cancer cells, the stabilization of TOP2B-DNA cleavage complexes in cardiomyocytes is a major driver of drug-induced cardiotoxicity. Research indicates that the resulting DNA double-strand breaks and subsequent mitochondrial interference lead to the heart failure often seen in patients receiving long-term chemotherapy. Consequently, TOP2B is a focal point for developing cardioprotective strategies and more selective anti-cancer agents.

Other names

TOP2B cleavage complexTopoisomerase II beta-DNA covalent complexTOP2B-DNA complexType IIB topoisomerase-DNA complex

Topoisomerase II poisons stabilize the transient covalent complex between the enzyme and DNA, preventing the re-ligation of the double-strand break and leading to permanent DNA damage and apoptosis.