{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe INO80 chromatin‐remodeling complex is a highly conserved, multisubunit ATPase that catalyzes dynamic alterations of nucleosome structure. Structural and biochemical studies have revealed that the INO80 complex is organized into distinct functional modules—comprising the Ino80 catalytic subunit, AAA+ proteins (Tip49a/Tip49b), actin‐related proteins, and additional metazoan‐specific factors—that cooperate to drive processes such as nucleosome sliding, spacing, and histone exchange. High‐resolution structural analyses and reconstitution experiments have delineated novel arrangements of its motor domains and accessory subunits, as well as uncovered a direct DNA binding activity mediated by conserved domains."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nINO80 performs essential roles in genome maintenance through its functions in DNA replication and repair. During S phase, it is recruited to replication origins and forks to promote efficient fork progression, stabilize stalled replisomes, and facilitate replication restart under stress. Moreover, INO80 contributes to DNA double‐strand break repair by mediating 5′–3′ resection and is important for interstrand crosslink repair in cooperation with factors such as FANCM and checkpoint regulators (ATR/ATM). Its stability and activity are fine‑tuned by post‑translational modifications and interactions with ubiquitin system components—for example, by the deubiquitinating enzyme BAP1 and the E3 ligase CHIP—which together safeguard genome integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in preserving genome integrity, INO80 is a key regulator of transcription. Acting as an essential coactivator when recruited by transcription factors such as Yin‑Yang‑1 (YY1), INO80 facilitates access to promoter and enhancer regions, modulating the expression of genes involved in cell cycle progression (for example, through regulation of p21 in a p53‑dependent manner). These transcriptional functions extend to oncogenic contexts where INO80 contributes to super‑enhancer activity and tumor‐promoting transcriptional programs in malignancies such as melanoma, lung, and cervical cancers. Moreover, composition of the INO80 complex can be dynamically modulated by interacting non‑coding RNAs and SUMOylation machinery, thereby tailoring its activity in different cellular contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its central roles in chromatin remodeling, INO80 influences developmental processes and tissue homeostasis. For example, proper INO80 function is critical for trophoblast cell viability, migration, and invasion—aspects that are essential for normal embryogenesis and have been linked with reproductive outcomes such as recurrent miscarriage. Collectively, these studies underscore the multifaceted roles of INO80 in orchestrating chromatin dynamics to regulate DNA replication, repair, and transcription, thereby ensuring genome stability and appropriate gene expression in both normal physiology and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jingji Jin, Yong Cai, Tingting Yao, et al. 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