{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHuman topoisomerase IIβ (TOP2B) plays a pivotal role in modulating DNA topology during transcription. It facilitates rapid, signal‐dependent gene activation by generating transient double‐stranded DNA breaks that promote local chromatin remodeling and permit nuclear receptor–mediated transcription. In doing so, TOP2B interacts with multifunctional transcription factors and cofactors—such as retinoic acid receptor α, nuclear respiratory factor 1 and the SWI/SNF complex—to coordinate the formation and repair of these breaks, thereby linking DNA damage–response pathways to regulated gene expression. This catalytic function is central not only to relieving torsional stress during transcription but also to ensuring appropriate promoter clearance and transcript elongation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDistinct from its closely related isoform TOP2A, which is critical for cell proliferation, TOP2B is dispensable for cell division yet essential in post‐mitotic contexts such as neuronal development and differentiation. Its expression is dynamically regulated in differentiating cells and appears to influence the transcription of long neural genes. Moreover, studies show that TOP2B’s nuclear localization and mobility are tightly controlled—features that likely underpin its role in developmental gene regulation and maintenance of genomic stability during lineage commitment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its developmental roles, TOP2B is a critical determinant of cellular responses to chemotherapeutic agents and other genotoxic stresses. It is targeted by topoisomerase poisons that induce covalent TOP2B–DNA cleavage complexes—events implicated in treatment‐related secondary malignancies and drug‐induced cardiotoxicity—and its natural amino acid variants can modulate cellular sensitivity to such drugs. Furthermore, TOP2B function is influenced by post‐translational modifications and interactions with kinases (for example, PKCζ), which alter its catalytic activity and stability, while its involvement in viral genome maintenance and innate immune responses further underscores its multifaceted regulatory significance. Structural studies have provided detailed insights into the ATPase domain of TOP2B, reinforcing its importance as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hai Xiao, Yong Mao, Shyamal D Desai, et al. 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