{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Histone variant H2AX is a central mediator of the DNA damage response, functioning as an early signaling platform that couples chromatin modifications to DNA repair. In response to double‐strand breaks, H2AX becomes rapidly phosphorylated on serine 139 (γ–H2AX), which in turn promotes the assembly and retention of repair proteins—including MDC1, Nbs1, and 53BP1—at sites of damage, thereby facilitating both checkpoint activation and efficient repair processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond serving as a recruitment platform, H2AX contributes to genomic stability as a dosage‐dependent “caretaker” that prevents aberrant repair and chromosomal translocations. Loss or haploinsufficiency of H2AX leads to compromised genomic integrity and increased tumorigenesis, underscoring its importance in suppressing cancer development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n H2AX is also implicated in specialized chromatin remodeling events. For instance, its phosphorylation is required for proper sex chromosome condensation and meiotic sex chromosome inactivation during spermatogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while regulation of its phosphorylation status—involving factors that modulate both serine and tyrosine residues—can influence the balance between engaging DNA repair and promoting apoptotic pathways. Recent studies have revealed that dynamic changes in the H2AX phosphorylation status, including dephosphorylation of a constitutive tyrosine (Tyr142) by damage‐responsive phosphatases such as EYA, as well as its phosphorylation by kinases that harbor unconventional kinase domains (e.g. WSTF), serve as critical molecular switches in this decision‐making process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Thus, H2AX functions not only as a marker of DNA damage but also as an active regulator of chromatin structure and DNA repair factor assembly, ensuring genome integrity and proper cell fate decisions following genotoxic stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Arkady Celeste, Simone Petersen, Peter J Romanienko, et al. 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