DNA topoisomerase 2-alpha and DNA topoisomerase 2-beta (TOP2A and TOP2B)

DNA topoisomerase 2-alpha and 2-beta are ATP-dependent homodimeric enzymes responsible for regulating DNA topology in eukaryotic cells by inducing transient double-strand breaks in DNA, allowing passage of another DNA duplex to relieve torsional strain and entanglement during replication, transcription, and chromosome segregation. Topoisomerase IIα (TOP2A) is essential for cell division and highly expressed during mitosis, concentrated in mitotic chromosomes, and serves as a key target for cancer chemotherapeutics such as etoposide and anthracyclines. Topoisomerase IIβ (TOP2B), while not essential for all cell types, plays roles in transcriptional regulation, especially in neural development, and mutations can lead to immunodeficiency or neurodevelopmental disorders. Both isoforms have homologous catalytic domains, but distinct C-terminal regions confer differential functions and cellular localization during the cell cycle. Drug targeting of these enzymes can lead to DNA damage and cytotoxicity, but may also cause serious side effects such as secondary cancers, resistance, and organ toxicity.

Other names

DNA topoisomerase IIα (TOP2A)DNA topoisomerase IIβ (TOP2B)Topoisomerase II alphaTopoisomerase II betaType II DNA topoisomerases

Stabilization of the DNA-topoisomerase II cleavage complex, leading to DNA double-strand breaks and cell death. Catalytic inhibition of ATPase activity (e.g., bisdioxopiperazines like ICRF-193 target the ATPase domain).