{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CIZ1 (CDKN1A‐interacting zinc finger protein 1) is a multifunctional nuclear protein that plays a central role in coordinating DNA replication and cell‐cycle progression. It is tethered to the nuclear matrix where it localizes to discrete replication foci, interacting with key cell‐cycle regulators such as cyclin A–CDK2 and p21^Cip1/Waf1 to facilitate the initiation of DNA synthesis at the G1/S transition (3,7,8). In addition, CIZ1 directly associates with components of the replication machinery – for example, via its N‑terminal replication domain and a C‑terminal nuclear matrix–anchoring domain – thereby promoting proper replisome formation and efficient S phase entry (3,8,9)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its well‐established role in DNA replication, CIZ1 is also implicated in the regulation of chromatin organization. In female cells, CIZ1 is recruited by the long noncoding RNA Xist through direct interactions with defined RNA motifs, ensuring stable localization of Xist to the inactive X chromosome and thereby contributing to the maintenance of epigenetic silencing (2,10). Notably, the formation of large RNA–protein assemblies by CIZ1 at the inactive X is modulated by alternatively spliced prion‐like domains, highlighting how structural heterogeneity can affect its subnuclear distribution and function (10).\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Deregulation of CIZ1 function is linked to human disease. Certain CIZ1 mutations and splice variants have been associated with neurological disorders such as dystonia, possibly by perturbing neurodevelopment or altering G1/S checkpoint regulation in neural cells (1,6). In parallel, aberrant expression and alternative splicing of CIZ1 are recurrent features in the context of cancer, where CIZ1 overexpression correlates with enhanced cell proliferation, altered cell‐cycle control, and activation of oncogenic signaling pathways such as β–catenin/TCF and YAP/TAZ (11,12,13). Together, these studies not only underscore the critical role of CIZ1 in normal cell proliferation and chromatin regulation but also point to its potential as a diagnostic biomarker and therapeutic target in a range of pathologies.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n "}, {"type": "b", "children": [{"type": "t", "text": "Citations:"}]}, {"type": "t", "text": "<br>\n (1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", \n (2)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", \n (3)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", \n (4)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", \n (5)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", \n (6)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", \n (7)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", \n (8)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", \n (9)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", \n (10)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", \n (11)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", \n (12)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", \n (13)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jianfeng Xiao, Ryan J Uitti, Yu Zhao, et al. 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