{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSASS6 (also known as SAS‐6) is a highly conserved coiled‐coil protein that forms the structural foundation of the centriole by self‐assembling into a cartwheel structure with ninefold symmetry. This early cartwheel assembly is essential for accurate daughter centriole (or procentriole) formation and is initiated by the timely recruitment of SASS6 in coordination with key regulators such as ZYG‐1/PLK4, STIL, and SAS‐5, as observed in both Caenorhabditis elegans and human cells. Through its oligomerization and interaction with other centriole duplication factors, SASS6 dictates the overall architecture and number of centrioles, thereby ensuring faithful centrosome duplication and genomic stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe function and cellular levels of SASS6 are tightly controlled through an intricate network of protein–protein interactions and regulated turnover during the cell cycle. Its association with proteins such as STIL, CPAP, and CEP135 helps steer not only cartwheel assembly but also subsequent centriole elongation, while specific domains (for example, the C‐terminal region) further mediate microtubule nucleation by linking to components of the γ‐tubulin ring complex. In parallel, ubiquitin ligases including FBXW5 and FBXW7, whose activities are modulated by kinases like PLK4, target SASS6 for proteolysis, thus ensuring that centriole duplication occurs only once per cell cycle."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of SASS6 has significant clinical implications. Hypomorphic or loss‐of‐function mutations in the SASS6 gene have been linked to primary autosomal recessive microcephaly—underscoring its critical role in brain development—whereas overexpression promotes centrosome amplification, mitotic errors, and chromosomal instability in cancer. Indeed, elevated SASS6 levels have been associated with colorectal, lung, and breast cancers, and aberrant interactions with transcriptional regulators involved in multiciliogenesis extend its influence beyond centrosome biology. Collectively, these findings emphasize that both insufficient and excessive SASS6 activity can disturb the delicate balance of centriole duplication, implicating its pivotal role in maintaining cellular homeostasis and genomic integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sebastian Leidel, Marie Delattre, Lorenzo Cerutti, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2282"}], "href": "https://doi.org/10.1038/ncb2282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21725316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21725316"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chieh-Ju C Tang, Shin-Yi Lin, Wen-Bin Hsu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SASS6 promotes tumor proliferation and is associated with TP53 and immune infiltration in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10238-024-01510-0"}], "href": "https://doi.org/10.1007/s10238-024-01510-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39443355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39443355"}]}]}]}