{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DONSON is emerging as a multifunctional factor that plays dual roles in normal development and in cancer. Its canonical function in safeguarding replication fork integrity and coordinating DNA damage responses ensures proper cell cycle progression and maintenance of genomic stability. In several studies, loss‐of‐function and genetic screening approaches have established that DONSON is indispensable for centrosomal function and efficient DNA repair, thereby preventing genomic instability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the context of development, germline mutations in DONSON result in severe disorders characterized by microcephaly, primordial dwarfism, and skeletal anomalies observed in syndromes such as Meier–Gorlin and Seckel-like phenotypes, underscoring its essential role during early embryogenesis and corticogenesis"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "5"}]}, {"type": "t", "text": "\n <br /><br />\n In parallel, aberrant expression of DONSON and its circular RNA isoform (circ‐DONSON) has been implicated in tumorigenesis. In gastric cancer, circ‐DONSON promotes tumor progression by recruiting chromatin remodeling complexes to the promoter of key transcription factors such as SOX4, thereby enhancing cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Overexpression of DONSON has also been linked to aggressive phenotypes in clear cell renal cell carcinoma and prostate cancer, while its deregulation contributes to chemoresistance—as demonstrated by cisplatin‐resistant models of gastric cancer and radioresistance in breast cancer"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n <br /><br />\n Collectively, these findings indicate that DONSON functions as a critical guardian of genome integrity in dividing cells. When its function is lost or deregulated, the consequences vary from developmental defects to enhanced tumor aggressiveness and therapy resistance. Understanding the molecular mechanisms underlying DONSON’s roles in replication, DNA repair, and transcriptional regulation may therefore provide valuable insights for the development of novel diagnostic biomarkers and therapeutic strategies in both congenital disorders and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Florian Fuchs, Gregoire Pau, Dominique Kranz, et al. 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