DNA topoisomerase 2-beta–DNA cleavage complex (TOP2B–DNA CC)

DNA topoisomerase 2-beta (TOP2B) is a member of the type II topoisomerase family that regulates DNA topology by generating transient double-strand breaks (PMID: 19456224). The TOP2B–DNA cleavage complex represents a critical catalytic intermediate where the enzyme is covalently linked to the DNA backbone via a phosphotyrosyl bond (PMID: 21964334). Unlike the alpha isoform (TOP2A), which is primarily associated with DNA replication in proliferating cells, TOP2B is expressed in post-mitotic cells and is essential for regulated gene transcription (PMID: 23103913). Therapeutic agents known as topoisomerase II poisons, such as etoposide and doxorubicin, act by stabilizing this cleavage complex, preventing the re-ligation of DNA and leading to the accumulation of permanent double-strand breaks (PMID: 25014433). While this mechanism is effective for inducing apoptosis in cancer cells, the stabilization of TOP2B–DNA complexes in cardiomyocytes is a primary driver of anthracycline-induced cardiotoxicity (PMID: 23103913). This complex is also implicated in the development of secondary malignancies and potential neurotoxicity due to its role in maintaining genomic integrity during transcription in the central nervous system (PMID: 21964334).

Other names

Topoisomerase II beta–DNA cleavage complexTOP2B–DNA covalent complexTOP2B–DNA adductTOP2B-DNA CCTopoisomerase II beta-DNA complex

Topoisomerase II poisons stabilize the transient TOP2B–DNA cleavage complex by inhibiting the re-ligation step of the catalytic cycle, effectively converting the enzyme into a cellular toxin that generates permanent DNA double-strand breaks (PMID: 19456224, PMID: 25014433).