DNA topoisomerase II beta–DNA cleavable complex (TOP2B–DNA complex)

DNA topoisomerase II beta (TOP2B) is an essential enzyme that regulates DNA topology by generating transient double-strand breaks to allow the passage of one DNA duplex through another (UniProt P23122). The Topoisomerase II beta–DNA cleavable complex is the specific catalytic intermediate where the enzyme is covalently linked to the 5' phosphate ends of the broken DNA (Nitiss, Nat Rev Cancer 2009). This complex is the primary pharmacological target for "topoisomerase poisons" such as etoposide and doxorubicin, which stabilize the complex and prevent DNA religation (Pommier et al., Chem Rev 2010). Unlike its isoform Topoisomerase II alpha, TOP2B is expressed in quiescent and post-mitotic cells, including cardiomyocytes and neurons, where it facilitates transcription (Zhang et al., Nat Med 2012). The stabilization of TOP2B–DNA complexes in heart tissue is recognized as the fundamental mechanism behind anthracycline-induced cardiotoxicity, leading to mitochondrial dysfunction and heart failure (Zhang et al., Nat Med 2012). Understanding this complex is vital for the development of next-generation chemotherapeutics that aim to maintain anti-tumor efficacy while reducing life-threatening side effects.

Other names

TOP2B-DNA covalent complexTopoisomerase II beta-DNA adductTOP2B-DNA cleavage complexTopoisomerase II beta-DNA cleavable complex

Stabilization of the covalent DNA-protein intermediate (cleavable complex), inhibiting DNA religation and inducing double-strand breaks.