{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BRCC36 is a zinc‐dependent deubiquitinating enzyme (DUB) belonging to the JAMM/MPN+ family that specifically cleaves lysine‐63–linked polyubiquitin chains. It plays a pivotal role in the DNA damage response by regulating the ubiquitin signals generated at double‐strand breaks, thereby modulating chromatin structure and the recruitment of repair factors. In the nucleus, BRCC36 is a core component of the BRCA1–A complex where, in association with adaptor proteins such as Abraxas, RAP80, MERIT40, and BRCC45, it ensures proper deubiquitination of substrates, which is essential for controlling DNA repair, cell cycle checkpoint activation, and maintenance of genomic stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " \n In addition, BRCC36 also functions in the cytoplasm within the BRISC complex where its activity and subcellular localization are governed by distinct scaffold proteins. Biochemical and structural studies reveal that BRCC36 requires assembly with pseudo DUB partners and higher‐order dimerization (super dimerization) for full catalytic activity and proper substrate recognition."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Furthermore, detailed analyses have shown that the modularity of BRCC36-containing complexes—as illustrated by studies on its regulation and complex assembly—is critical for its function in orchestrating ubiquitin-dependent signaling during DNA double-strand break repair."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": " Disruption of BRCC36 function, whether by mutations in the BRCA1–A/BRISC complex components or by altered complex integrity and localization, leads to defective deubiquitination at sites of DNA damage, impaired checkpoint control, and genomic instability, thus contributing to tumorigenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bijan Sobhian, Genze Shao, Dana R Lilli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1139516"}], "href": "https://doi.org/10.1126/science.1139516"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17525341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17525341"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bin Wang, Stephen J Elledge "}, {"type": "b", "children": [{"type": "t", "text": "Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0710061104"}], "href": "https://doi.org/10.1073/pnas.0710061104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18077395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18077395"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuanshu Dong, Mohamed-Ali Hakimi, Xiaowei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(03)00424-6"}], "href": "https://doi.org/10.1016/s1097-2765(03"}, {"type": "t", "text": "00424-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14636569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14636569"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Eric M Cooper, Colleen Cutcliffe, Troels Z Kristiansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.27"}], "href": "https://doi.org/10.1038/emboj.2009.27"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19214193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19214193"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bin Wang, Kristen Hurov, Kay Hofmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1770309"}], "href": "https://doi.org/10.1101/gad.1770309"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19261749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19261749"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lin Feng, Jun Huang, Junjie Chen "}, {"type": "b", "children": [{"type": "t", "text": "MERIT40 facilitates BRCA1 localization and DNA damage repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1770609"}], "href": "https://doi.org/10.1101/gad.1770609"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19261748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19261748"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Genze Shao, Jeffrey Patterson-Fortin, Troy E Messick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1739609"}], "href": "https://doi.org/10.1101/gad.1739609"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19261746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19261746"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lin Feng, Jiadong Wang, Junjie Chen "}, {"type": "b", "children": [{"type": "t", "text": "The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.135392"}], "href": "https://doi.org/10.1074/jbc.M110.135392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20656690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20656690"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Julius Rabl, Richard D Bunker, Andreas D Schenk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2019.06.002"}], "href": "https://doi.org/10.1016/j.molcel.2019.06.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31253574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31253574"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Elton Zeqiraj, Lei Tian, Christopher A Piggott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2015.07.028"}], "href": "https://doi.org/10.1016/j.molcel.2015.07.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26344097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26344097"}]}]}]}