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Shelterin (also called telosome) is a protein complex known to protect mammalian telomeres from DNA repair mechanisms, as well as regulate telomerase activity. In mammals and other eukaryotes, telomeric DNA consists of double- and single-stranded TTAGGG repeats and a single-stranded, G-rich overhang. Subunits of shelterin bind to these regions and induce the formation of a t-loop, a cap structure that deters DNA-damage-sensing machinery from mistakenly repairing telomeres. The absence of shelterin causes telomere uncapping and thereby activates damage-signaling pathways that may lead to non-homologous end joining (NHEJ), homology directed repair (HDR),〔Rodriguez, Raphaël, Sebastian Müller, Justin A. Yeoman, Chantal Trentesaux, Jean-Françios Riou, and Shankar Balasubramanian. “A Novel Small Molecule That Alters Shelterin Integrity and Triggers a DNA-Damage Response at Telomeres.” Journal of the American Chemical Society 130 (2008): 15758-59. doi: 10.1021/ja805615w.〕 senescence, or apoptosis.〔Palm, Wilhelm, and Titia de Lange. “How Shelterin Protects Mammalian Telomeres.” Annual Reviews 42 (2008): 301-34. doi: 10.1146/annurev.genet.41.110306.130350.〕 ==Subunits== Shelterin has six subunits: TRF1, TRF2, POT1, RAP1, TIN2, and TPP1.〔Xin, Huawei, Dan Liu, and Zhou Songyang. “The telomere/shelterin complex and its functions.” Genome Biology 9 (2008): 232.〕 They can operate in smaller subsets to regulate the length of or protect telomeres. * TRF1 (Telomere Repeat Factor 1): TRF1 is a homodimeric protein〔de Lange, Titia. “How Shelterin Solves the Telomere End-Protection Problem.” Cold Spring Harbor Symposia on Quantitative Biology 75 (2010): 167-77. doi: 10.1101/sqb.2010.75.017.〕 that binds to the double-stranded TTAGGG region of the telomere. It may recruit PINX1 to inhibit telomere elongation by telomerase.〔 * TRF2 (Telomere Repeat Factor 2): TRF2 is a homodimeric protein〔that binds to the double-stranded TTAGGG region of the telomere and prevents the recognition of double-strand DNA breaks.〔Choi, Kyung H., Amy S. Farrell, Amanda S. Lakamp, and Michel M. Ouellette. “Characterization of the DNA binding specificity of Shelterin complexes.” Nucleic Acids Research 39 (2011): 9206-23. doi 10.1093/nar/gkr665.〕 * POT1 (Protection of Telomere 1): POT1 contains oligonucleotide/oligosaccharide binding folds, which increase its affinity for single-stranded TTAGGG region of telomeric DNA. POT1 prevents the degradation of this single stranded DNA by nucleases and shelters the G-overhang.〔 * RAP1 (Repressor / Activator Protein 1): RAP1 is a stabilizing protein associated with TRF2. * TIN2 (TRF1- and TRF2-Interacting Nuclear Protein 2): TIN2 is a stabilizing protein that binds to the TPP1-POT1 complex, TRF1, and TRF2,〔Takai, Kaori K., Sarah Hooper, Stephanie Blackwood, Rita Gandhi, and Titia de Lange. “In Vivo Stoichiometry of Shelterin Components.” Journal of Biological Chemistry 285 (2010): 1457-67. doi: 10.1074/jbc.M109.038026.〕 thereby bridging units attached to double-stranded DNA and units attached to single-stranded DNA.〔 * TPP1 (TINT1, PTOP, PIP1): TPP1 is a protein associated with POT1. The loss of TPP1 leads to impaired POT1 function.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Shelterin」の詳細全文を読む スポンサード リンク
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