DNA topoisomerase 2-alpha (TOP2A)

DNA topoisomerase 2-alpha (TOP2A) is a critical nuclear enzyme that regulates the topological state of DNA by inducing transient double-strand breaks, allowing one DNA duplex to pass through another before resealing the break (UniProt P11388). This activity is essential for resolving DNA knots and catenanes that form during replication, transcription, and chromosome segregation in mitosis (Wikipedia). TOP2A is highly expressed in rapidly proliferating cells, making it a prominent therapeutic target for several classes of anticancer drugs, including anthracyclines and epipodophyllotoxins (PubMed PMID: 1400139). These agents typically act as topoisomerase poisons by stabilizing the enzyme-DNA cleavage complex, which leads to the accumulation of lethal DNA damage and subsequent apoptosis (NIH). However, targeting TOP2A is associated with significant clinical challenges, such as cardiotoxicity and the risk of secondary leukemias due to chromosomal translocations (PubMed PMID: 10409239). Consequently, TOP2A expression and gene status are frequently evaluated as biomarkers for tumor proliferation, prognosis, and therapeutic response (GeneCards).

Other names

TOP2ADNA topoisomerase II alphaTP2ATOPIIADNA topoisomerase 2-alphaDNA topoisomerase II alpha 170kDa

Topoisomerase II poisons stabilize the covalent enzyme-DNA cleavage complex, preventing DNA relegation and leading to double-strand breaks; catalytic inhibitors block the enzyme's biochemical cycle (e.g., ATP hydrolysis) without increasing DNA cleavage (PubMed PMID: 1400139).