DNA topoisomerase II alpha (TOP2A) (TOP2A)

DNA topoisomerase II alpha (TOP2A) is a vital nuclear enzyme that regulates DNA topology by inducing transient double-strand breaks, allowing the passage of one DNA duplex through another [7, 11]. This catalytic activity is essential for critical cellular processes, including DNA replication, transcription, and the segregation of daughter chromosomes during mitosis [9, 16]. Because it creates double-strand breaks, TOP2A is intrinsically hazardous to genomic integrity and is strictly regulated within the cell [14, 16]. In many cancers, TOP2A is overexpressed, making it a major therapeutic target for several classes of chemotherapy drugs [6, 13]. These drugs, known as topoisomerase II poisons (e.g., etoposide and doxorubicin), act by stabilizing the covalent enzyme-DNA complex, preventing DNA religation and leading to the accumulation of lethal double-strand breaks that trigger apoptosis [3, 16]. Other agents, termed catalytic inhibitors, interfere with the enzyme's turnover without trapping the cleavage complex [4, 13]. Despite their efficacy, these agents are associated with significant safety concerns, such as cardiotoxicity and the risk of secondary malignancies like therapy-related acute myeloid leukemia [9, 14]. TOP2A expression levels and gene amplification are often used as biomarkers to predict drug sensitivity and patient prognosis [6, 13].

Other names

DNA topoisomerase 2-alphaTopo II alphaDNA topoisomerase II 170 kDaTOP2

Topoisomerase II poisons stabilize the covalent enzyme-DNA cleavage complex, preventing DNA religation and leading to lethal double-strand breaks; catalytic inhibitors interfere with the enzyme's catalytic cycle without trapping the cleavage complex [3, 4, 13, 16].