DNA topoisomerase 2-beta (TOP2B)-DNA cleavable complex (TOP2B-DNA CC)

DNA topoisomerase 2-beta (TOP2B) is a critical enzyme that regulates DNA topology by inducing transient double-strand breaks to allow the passage of one DNA duplex through another (UniProt P23122). The TOP2B-DNA cleavable complex represents a catalytic intermediate where the enzyme is covalently tethered to the DNA backbone. While this state is typically transient, it is the primary target for a class of anticancer drugs known as topoisomerase II poisons, such as etoposide and doxorubicin (Nitiss, 2009, Nature Reviews Cancer). These drugs stabilize the complex, preventing the religation of DNA and converting the enzyme into a source of lethal DNA damage. Unlike the TOP2A isoform, TOP2B is expressed in non-dividing cells, making its stabilization in cardiomyocytes a major cause of drug-induced heart failure (Zhang et al., 2012, Nature Medicine). This cardiotoxicity is a significant limiting factor in the clinical use of anthracyclines. Research into the TOP2B-DNA cleavable complex also suggests its involvement in the transcription of long genes associated with neurodevelopment and neurodegeneration (Madabhushi et al., 2015, Cell). Consequently, the TOP2B-DNA cleavable complex is a focal point for both therapeutic efficacy in oncology and the management of severe treatment-related side effects.

Other names

TOP2B-DNA covalent complexTopoisomerase II beta cleavage complexTOP2B-DNA adductTOP2B-DNA phosphotyrosyl complex

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