{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHAF1A, the p150 subunit of the chromatin assembly factor‐1 (CAF-1) complex, plays a pivotal role in depositing histone H3/H4 dimers during DNA replication and in maintaining chromatin structure. In addition to its classical function in nucleosome assembly, CHAF1A contributes to the preservation of somatic cell identity and acts as a barrier to cell fate reprogramming by restricting chromatin accessibility at key enhancer elements."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, elevated CHAF1A expression is frequently observed in several malignancies. In neuroblastoma, for instance, gain-of-function of CHAF1A sustains a poorly differentiated state and supports oncogenesis—partly by upregulating polyamine metabolism, which promotes cell proliferation and blocks neuronal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In epithelial ovarian cancer, high levels of CHAF1A are strongly associated with advanced stage, lymph node metastasis, and reduced apoptosis, thereby augmenting tumor cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in colon cancer, aberrant CHAF1A overexpression correlates with advanced tumor invasion and poor patient survival"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and in gastric cancer, CHAF1A functions as a co-activator in the Wnt pathway to enhance oncogenic targets such as c-MYC and CCND1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Further evidence from glioblastoma studies shows that CHAF1A supports tumor cell proliferation via the AKT/FOXO3a/Bim axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and that its modulation by tumor-suppressive microRNAs can reduce tumor viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in proliferation and differentiation, CHAF1A is involved in the maintenance of chromosomal and nucleolar architecture. An N-terminal fragment of p150 is sufficient to regulate nucleolar associations with specific chromosomal regions, underscoring a separable function of CHAF1A in organizing nuclear domains."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In the context of DNA repair, CHAF1A transiently dissociates from chromatin during the repair of oxidative base damage, thereby permitting efficient base excision repair before re-establishing chromatin structure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these studies highlight CHAF1A as a multifunctional protein whose deregulation not only perturbs chromatin assembly and genomic integrity but also contributes to tumor progression and represents an attractive target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sihem Cheloufi, Ulrich Elling, Barbara Hopfgartner, et al. 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