DNA topoisomerase II alpha (TOP2A)

DNA topoisomerase II alpha (TOP2A) is a nuclear enzyme essential for the maintenance and regulation of DNA topology in eukaryotic cells. It functions as a homodimer, introducing transient double-strand breaks in DNA to resolve tangles and supercoils, thereby facilitating vital cellular processes such as DNA replication, transcription, chromosome condensation, and segregation during mitosis. TOP2A is highly expressed in proliferating cells, especially during mitosis, making it a key biomarker for cell proliferation and a prominent target for anticancer drugs known as topoisomerase II poisons. Inhibition or mutation of TOP2A disrupts its decatenation function, leading to genomic instability and potential cell death. Clinically, altered TOP2A expression and mutation are implicated as biomarkers and determinants of prognosis, therapeutic response, and drug resistance in several cancers[2][3][4][5][6][7].

Other names

Topoisomerase 2-alphaTOP2αDNA topoisomerase II alphaTopo IIα

Drugs target TOP2A to induce DNA double-strand breaks by stabilizing the cleavage complex (enzyme-DNA covalent intermediate), leading to apoptosis in proliferating cells; inhibition of decatenation and chromosome segregation; secondary mechanisms may involve generation of DNA damage or induction of mutations[3][4][5].