Shelterin

Shelterin (also called telosome) is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences (2-15 kilobases in humans) along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 nucleotide 3' (G-strand) overhang.[1][2] Much of the final double-stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) overhang to form a small D-loop (Displacement-loop).[1][3]

The absence of shelterin causes telomere uncapping and thereby activates damage-signaling pathways[4] that may lead to non-homologous end joining (NHEJ), homology directed repair (HDR),[5] end-to-end fusions,[6] genomic instability,[6] senescence, or apoptosis.[7]

  1. ^ a b de Lange, Titia (2010). "How Shelterin Solves the Telomere End-Protection Problem". Cold Spring Harbor Symposia on Quantitative Biology. 75: 167–77. doi:10.1101/sqb.2010.75.017. PMID 21209389. S2CID 18644661.
  2. ^ Červenák F, Juríková K, Nosek J, Tomáška L (2017). "Double-stranded telomeric DNA binding proteins: Diversity matters". Cell Cycle. 16 (17): 1568–1577. doi:10.1080/15384101.2017.1356511. PMC 5587031. PMID 28749196.
  3. ^ Greider, Carol (1999). "Telomeres do D-loop-T-loop". Cell. 97 (4): 419–422. doi:10.1016/S0092-8674(00)80750-3. PMID 10338204.
  4. ^ Zhu Y, Liu X, Geng X (2019). "Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction". Biogerontology. 20 (1): 1–16. doi:10.1007/s10522-018-9769-1. PMID 30229407.
  5. ^ Rodriguez, Raphaël; Müller, Sebastian; Yeoman, Justin A.; Trentesaux, Chantal; Riou, Jean-Françios; Balasubramanian, Shankar (2008). "A Novel Small Molecule That Alters Shelterin Integrity and Triggers a DNA-Damage Response at Telomeres". Journal of the American Chemical Society. 130 (47): 15758–59. doi:10.1021/ja805615w. PMC 2746963. PMID 18975896.
  6. ^ a b Jones M, Bisht K, Savage SA, Nandakumar J, Keegan CE, Maillard I (2016). "The shelterin complex and hematopoiesis". Journal of Clinical Investigation. 126 (3): 1621–1629. doi:10.1172/JCI84547. PMC 4855927. PMID 27135879.
  7. ^ Palm W, de Lange T (2008). "How Shelterin Protects Mammalian Telomeres". Annual Review of Genetics. 42: 301–34. doi:10.1146/annurev.genet.41.110306.130350. PMID 18680434.