DNA topoisomerase 2-beta (TOP2B) (TOP2B)

DNA topoisomerase 2-beta (TOP2B) is an essential enzyme that regulates DNA supercoiling and entanglement by creating transient double-strand breaks through which another DNA duplex is passed (UniProt P11388). Unlike its isoform TOP2A, which is primarily expressed during cell division, TOP2B is constitutively expressed in both proliferating and quiescent cells, including cardiomyocytes and neurons (Zhang et al., 2012, Nature Medicine). It is particularly involved in the transcription of long genes and the regulation of gene expression programs during development (Madabhushi et al., 2015, Cell). Many clinical anticancer drugs, such as anthracyclines and epipodophyllotoxins, act as topoisomerase II poisons by trapping the enzyme in a covalent complex with DNA, known as the TOP2B-DNA cleavage complex (TOP2Bcc) (Nitiss, 2009, Nature Reviews Cancer). While this mechanism is effective for killing cancer cells, the stabilization of TOP2Bcc in healthy tissues is strongly linked to severe side effects, most notably anthracycline-induced cardiotoxicity and the development of secondary leukemias (Zhang et al., 2012). Dexrazoxane is currently the only FDA-approved drug that mitigates this toxicity by preventing the formation of or helping to resolve these complexes.

Other names

Topoisomerase II betaTOP2BDNA topoisomerase II beta-DNA cleavage complexTOP2BccTOP2-BETA

Stabilization of the covalent DNA-protein cleavage complex (topoisomerase II poison), preventing DNA religation and inducing double-strand breaks (Nitiss, 2009, Nature Reviews Cancer).