{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNSMCE3 is an integral non‐SMC subunit of the SMC5/6 complex, a multi‐protein machine that safeguards chromosomal integrity by orchestrating the resolution of diverse DNA structures and facilitating accurate recombination events. Its incorporation into the SMC5/6 complex is essential for maintaining the stability of the entire assembly, as loss of individual non‐SMC components destabilizes the complex and compromises its function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that missense mutations in NSMCE3 are linked to a severe chromosome breakage syndrome. Affected individuals exhibit genomic instability characterized by chromosome rearrangements, micronuclei formation, and a defective homologous recombination repair process. Such mutations disrupt key inter-subunit interactions within the SMC5/6 complex, leading to cellular hypersensitivity to replication stress and DNA damage, which in turn compromises both T and B cell functions and predisposes patients to life-threatening pulmonary complications in early childhood."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in genome maintenance, NSMCE3 is positioned in a chromosomal region (proximal 15q) that is implicated in neurodevelopmental disorders. This genomic localization suggests that NSMCE3, like other imprinted genes in the area, might also contribute to developmental abnormalities and could be part of the broader molecular framework underlying syndromes such as Prader-Willi and Angelman, although its precise developmental functions remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elaine M Taylor, Alice C Copsey, Jessica J R Hudson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00767-07"}], "href": "https://doi.org/10.1128/MCB.00767-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18086888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18086888"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Saskia N van der Crabben, Marije P Hennus, Grant A McGregor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI82890"}], "href": "https://doi.org/10.1172/JCI82890"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27427983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27427983"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "T K Chibuk, J M Bischof, R Wevrick "}, {"type": "b", "children": [{"type": "t", "text": "A necdin/MAGE-like gene in the chromosome 15 autism susceptibility region: expression, imprinting, and mapping of the human and mouse orthologues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2156-2-22"}], "href": "https://doi.org/10.1186/1471-2156-2-22"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11782285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11782285"}]}]}]}