DNA-topoisomerase II alpha cleavage complex (TOP2A-DNA CC) (TOP2A-DNA CC)

DNA-topoisomerase II alpha (TOP2A) is a critical nuclear enzyme that manages DNA topology by creating transient double-strand breaks to allow the passage of one DNA duplex through another (Source: UniProt P11388). The cleavage complex is the specific intermediate state where the enzyme is covalently linked to the 5' ends of the broken DNA via a tyrosyl-phosphate bond (Source: Nitiss, J. L., Nat Rev Cancer, 2009). While this state is normally short-lived, it is the primary target for a class of chemotherapy drugs known as topoisomerase II poisons, such as etoposide and doxorubicin. These drugs stabilize the complex, preventing the religation of the DNA strands and effectively converting an essential enzyme into a cellular toxin (Source: Pommier, Y., Nat Rev Cancer, 2013). The resulting accumulation of permanent DNA double-strand breaks triggers apoptotic pathways, making it a potent strategy for treating rapidly dividing cancer cells. TOP2A is frequently overexpressed in various malignancies, correlating with high proliferation rates and serving as both a therapeutic target and a prognostic biomarker in oncology (Source: StatPearls, Topoisomerase Inhibitors).

Other names

Topoisomerase II alpha-DNA covalent complexTOP2A cleavage complexTOP2A-ccDNA-topoisomerase II alpha complex

Topoisomerase II poisons stabilize the transient covalent complex between the enzyme and DNA, preventing the religation of the DNA strands and leading to the formation of permanent double-strand breaks that trigger apoptosis (Source: Pommier, Y., Nat Rev Cancer, 2013).