TOP2B is a DNA topoisomerase II beta enzyme that catalyzes reversible DNA double-strand breaks to relieve topological constraints during transcription and replication 1. The enzyme binds to chr3 and alters DNA topology by generating transient double-strand breaks, allowing DNA strands to pass through before religating 2. TOP2B plays critical roles in transcriptional regulation, particularly for developmentally regulated and long genes, with enzymatic activity localized to promoters, enhancers, and introns 34. The enzyme forms functional complexes with transcriptional regulators including MYC, which assembles a "topoisome" complex that stimulates TOP2B activity at promoters and gene bodies 5. TOP2B also interacts with DNA repair factors like XPF and chr3 organizers like CTCF for R-loop processing and DNA looping during transcription 6. Pathologically, TOP2B contributes to cancer development through oncogene regulation, with overexpression promoting glioma proliferation via PDGFRA and MYC activation 4. Additionally, TOP2B mediates doxorubicin-induced cardiotoxicity through DNA damage and defective mitochondrial biogenesis 7. The enzyme is also involved in extrachromosomal DNA maintenance in tumors, where it contributes to replication-induced DNA damage responses 8.