{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe ACD gene, which encodes the telomeric protein TPP1, plays a pivotal role in telomere maintenance by directly regulating telomerase function. Structural studies have shown that the OB‐fold domain of TPP1 contains key elements—most notably the TEL patch—that mediate a specific interaction with telomerase, thereby both recruiting the enzyme to telomeres and markedly enhancing its repeat‐addition processivity. Disruption of this interface through mutation has been linked to telomere shortening and telomerase insufficiency in human disease, underscoring the centrality of ACD/TPP1 in governing telomerase action and telomere length homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in telomerase regulation, ACD/TPP1 is a core component of the shelterin complex that safeguards chromosome ends. Through direct interactions with POT1 and TIN2, TPP1 forms a heterodimer that not only “caps” the telomeric single‐stranded overhang but also bridges the duplex–binding factors to establish a functional telosome. Multiple reconstitution and structural studies have documented how discrete domains within TPP1 participate in assembling this multi‐protein complex—thereby preventing aberrant DNA repair activities while coordinating telomere length control—and how altered interactions (for example, via mutations) can predispose cells to genomic instability and even cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional layers of regulation further refine ACD/TPP1 function. Post‐translational modifications, alternative splice isoforms, and interactions with diverse regulatory factors (including kinases such as NEK6 and proteins like UPF1) modulate TPP1’s ability to engage telomerase in a cell cycle–dependent and stress‐responsive manner. Such dynamic regulation not only fine‐tunes telomere elongation and capping but also links defects in these processes to disorders ranging from bone marrow failure and dyskeratosis congenita to various cancers and even telomere dysfunction in chronic lung disease. Together, these studies reveal a complex regulatory network in which ACD/TPP1 integrates structural, enzymatic, and signal‐dependent inputs to maintain telomere integrity and genome stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huawei Xin, Dan Liu, Ma Wan, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Structure of active human telomerase with telomere shelterin protein TPP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-022-04582-8"}], "href": "https://doi.org/10.1038/s41586-022-04582-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35418675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35418675"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dan Liu, Amin Safari, Matthew S O'Connor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTOP interacts with POT1 and regulates its localization to telomeres."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1142"}], "href": "https://doi.org/10.1038/ncb1142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15181449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15181449"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Matthew S O'Connor, Amin Safari, Huawei Xin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0605303103"}], "href": "https://doi.org/10.1073/pnas.0605303103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16880378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16880378"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Dirk Hockemeyer, Wilhelm Palm, Tobias Else, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Telomere protection by mammalian Pot1 requires interaction with Tpp1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb1270"}], "href": "https://doi.org/10.1038/nsmb1270"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17632522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17632522"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Eladio Abreu, Elena Aritonovska, Patrick Reichenbach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00240-10"}], "href": "https://doi.org/10.1128/MCB.00240-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20404094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20404094"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Feng Wang, Ming Lei "}, {"type": "b", "children": [{"type": "t", "text": "Human telomere POT1-TPP1 complex and its role in telomerase activity regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Methods Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-1-61779-092-8_17"}], "href": "https://doi.org/10.1007/978-1-61779-092-8_17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21461822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21461822"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Helen Hwang, Noah Buncher, Patricia L Opresko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POT1-TPP1 regulates telomeric overhang structural dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2012.08.018"}], "href": "https://doi.org/10.1016/j.str.2012.08.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22981946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22981946"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Mark Corriveau, Michael R Mullins, Diane Baus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coordinated interactions of multiple POT1-TPP1 proteins with telomere DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.471896"}], "href": "https://doi.org/10.1074/jbc.M113.471896"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23616058"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23616058"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Sujay Ray, Jigar N Bandaria, Mohammad H Qureshi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G-quadruplex formation in telomeres enhances POT1/TPP1 protection against RPA binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1321436111"}], "href": "https://doi.org/10.1073/pnas.1321436111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24516170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24516170"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Alec N Sexton, Samuel G Regalado, Christine S Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.246819.114"}], "href": "https://doi.org/10.1101/gad.246819.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25128433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25128433"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Lauren G Aoude, Antonia L Pritchard, Carla Daniela Robles-Espinoza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/dju408"}], "href": "https://doi.org/10.1093/jnci/dju408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25505254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25505254"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Cory Rice, Prashanth Krishna Shastrula, Andrew V Kossenkov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional analysis of the human POT1-TPP1 telomeric complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms14928"}], "href": "https://doi.org/10.1038/ncomms14928"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28393830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28393830"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Cong Chen, Peili Gu, Jian Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms14929"}], "href": "https://doi.org/10.1038/ncomms14929"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28393832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28393832"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Benjamin R Houghtaling, Leanora Cuttonaro, William Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2004.08.052"}], "href": "https://doi.org/10.1016/j.cub.2004.08.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15380063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15380063"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Gaël Cristofari, Katarzyna Sikora, Joachim Lingner "}, {"type": "b", "children": [{"type": "t", "text": "Telomerase unplugged."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "ACS Chem Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/cb700037c"}], "href": "https://doi.org/10.1021/cb700037c"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17373762"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17373762"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Tian Tang, Fu-Xiang Zhou, Han Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of telomere-related proteins correlates with resistance to radiation in human laryngeal cancer cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or_00000381"}], "href": "https://doi.org/10.3892/or_00000381"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19424630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19424630"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Ma Wan, Jun Qin, Zhou Songyang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.021105"}], "href": "https://doi.org/10.1074/jbc.M109.021105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19648609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19648609"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Chrysa M Latrick, Thomas R Cech "}, {"type": "b", "children": [{"type": "t", "text": "POT1-TPP1 enhances telomerase processivity by slowing primer dissociation and aiding translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.409"}], "href": "https://doi.org/10.1038/emboj.2009.409"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20094033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20094033"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Robert Y L Zee, Paul M Ridker, Daniel I Chasman "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants in eleven telomere-associated genes and the risk of incident cardio/cerebrovascular disease: The Women's Genome Health Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Chim Acta (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cca.2010.10.003"}], "href": "https://doi.org/10.1016/j.cca.2010.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20937264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20937264"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "T de Lange "}, {"type": "b", "children": [{"type": "t", "text": "How shelterin solves the telomere end-protection problem."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cold Spring Harb Symp Quant Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/sqb.2010.75.017"}], "href": "https://doi.org/10.1101/sqb.2010.75.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21209389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21209389"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Adeline Augereau, Claire T'kint de Roodenbeke, Thomas Simonet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Telomeric damage in early stage of chronic lymphocytic leukemia correlates with shelterin dysregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-07-295774"}], "href": "https://doi.org/10.1182/blood-2010-07-295774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21355086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21355086"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Raghav Chawla, Sophie Redon, Christina Raftopoulou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2011.280"}], "href": "https://doi.org/10.1038/emboj.2011.280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21829167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21829167"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Yi Zhang, Liuh-Yow Chen, Xin Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1217733110"}], "href": "https://doi.org/10.1073/pnas.1217733110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23509301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23509301"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Lei Yang, Wenbo Wang, Liu Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Telomere-binding protein TPP1 modulates telomere homeostasis and confers radioresistance to human colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0081034"}], "href": "https://doi.org/10.1371/journal.pone.0081034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24260532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24260532"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Weiguang Qiang, Qinqin Wu, Fuxiang Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.02.001"}], "href": "https://doi.org/10.1016/j.bbrc.2014.02.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24513288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24513288"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Yun-Ling Zheng, Fan Zhang, Bing Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Telomerase enzymatic component hTERT shortens long telomeres in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.28705"}], "href": "https://doi.org/10.4161/cc.28705"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24721976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24721976"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Hande Kocak, Bari J Ballew, Kamlesh Bisht, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.248567.114"}], "href": "https://doi.org/10.1101/gad.248567.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25233904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25233904"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Tsz Wai Chu, Yasmin D'Souza, Chantal Autexier "}, {"type": "b", "children": [{"type": "t", "text": "The Insertion in Fingers Domain in Human Telomerase Can Mediate Enzyme Processivity and Telomerase Recruitment to Telomeres in a TPP1-Dependent Manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00746-15"}], "href": "https://doi.org/10.1128/MCB.00746-15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26503784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26503784"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Michael R Mullins, Malligarjunan Rajavel, Wilnelly Hernandez-Sanchez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POT1-TPP1 Binding and Unfolding of Telomere DNA Discriminates against Structural Polymorphism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2016.04.031"}], "href": "https://doi.org/10.1016/j.jmb.2016.04.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27173378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27173378"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Yugo Hirai, Miki Tamura, Junji Otani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NEK6-mediated phosphorylation of human TPP1 regulates telomere length through telomerase recruitment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gtc.12391"}], "href": "https://doi.org/10.1111/gtc.12391"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27396482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27396482"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Tanveer Ahmad, Isaac K Sundar, Ana M Tormos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shelterin Telomere Protection Protein 1 Reduction Causes Telomere Attrition and Cellular Senescence via Sirtuin 1 Deacetylase in Chronic Obstructive Pulmonary Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2016-0198OC"}], "href": "https://doi.org/10.1165/rcmb.2016-0198OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27559927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27559927"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Kamlesh Bisht, Eric M Smith, Valerie M Tesmer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional consequences of a disease mutation in the telomere protein TPP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1605685113"}], "href": "https://doi.org/10.1073/pnas.1605685113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27807141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27807141"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Sherilyn Grill, Kamlesh Bisht, Valerie M Tesmer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two Separation-of-Function Isoforms of Human TPP1 Dictate Telomerase Regulation in Somatic and Germ Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.05.073"}], "href": "https://doi.org/10.1016/j.celrep.2019.05.073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31216472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31216472"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Mengyuan Xu, Janna Kiselar, Tawna L Whited, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POT1-TPP1 differentially regulates telomerase via POT1 His266 and as a function of single-stranded telomere DNA length."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1905381116"}], "href": "https://doi.org/10.1073/pnas.1905381116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31685617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31685617"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Alessandro Cicconi, Sandy Chang "}, {"type": "b", "children": [{"type": "t", "text": "Shelterin and the replisome: at the intersection of telomere repair and replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Opin Genet Dev (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gde.2020.02.016"}], "href": "https://doi.org/10.1016/j.gde.2020.02.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32171974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32171974"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Zala Sekne, George E Ghanim, Anne-Marie M van Roon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of human telomerase recruitment by TPP1-POT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.abn6840"}], "href": "https://doi.org/10.1126/science.abn6840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35201900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35201900"}]}]}]}