{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EMSY is a large nuclear protein that plays multiple roles in chromatin‐ and transcription‐related processes, with important consequences in DNA repair and oncogenesis. Functionally, EMSY interacts directly with the N‐terminal region of BRCA2, thereby modulating its transactivation potential and influencing homologous recombination repair; indeed, EMSY overexpression can mimic BRCA2 deficiency and promote genomic instability, features that have been implicated in sporadic breast and ovarian cancers (1,9,10). Furthermore, EMSY is frequently amplified in these cancers and its increased expression is associated with poor clinical outcome, suggesting that it acts as an oncogene by interfering with normal DNA repair mechanisms (2,3,6,11). In addition to its effects on DNA repair, EMSY participates in transcriptional repression by forming complexes with chromatin regulators such as HP1β, BS69, and components of the Sin3/HDAC machinery; through these interactions, EMSY is recruited (for example by ETS‐1) to specific promoters where it delivers histone demethylases and suppresses the expression of tumor‐suppressive genes such as the antimetastatic microRNA miR‑31 (4,6). Moreover, EMSY is a phosphorylation substrate of Akt1, and this post‐translational modification relieves its repressive effects on interferon‐stimulated genes—a mechanism that may underlie aspects of immune regulation and contribute to the cellular response during viral infection and oncogenesis (5,7). Structural studies further reveal that EMSY contains domains capable of binding chromatin modifiers and mediating protein–protein interactions that are critical for its function in assembling repressive chromatin complexes (8). Collectively, the available data support a model in which EMSY, via its regulation of BRCA2 activity, chromatin signaling, and transcriptional repression, contributes to tumor development, influences patient prognosis, and may even affect responses to chemotherapy, particularly in cancers with homologous recombination defects (1,2,3,9,10,11).\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n (1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", (2)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", (3)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", (4)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", (5)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", (6)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", (7)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", (8)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", (9)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", (10)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", (11)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Luke Hughes-Davies, David Huntsman, Margarida Ruas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(03)00930-9"}], "href": "https://doi.org/10.1016/s0092-8674(03"}, {"type": "t", "text": "00930-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14651845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14651845"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lindsay A Brown, Steve E Kalloger, Melinda A Miller, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of a novel nuclear protein complex involved in nuclear hormone receptor-mediated gene regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M805872200"}], "href": "https://doi.org/10.1074/jbc.M805872200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19131338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19131338"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Scott A Ezell, Christos Polytarchou, Maria Hatziapostolou, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2014.01.029"}], "href": "https://doi.org/10.1016/j.molcel.2014.01.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24582497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24582497"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Antonio Marzio, Emma Kurz, Jennifer M Sahni, et al. 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