{"doi":"10.1128/mcb.00593-18","title":"TIN2 Functions with TPP1/POT1 To Stimulate Telomerase Processivity","abstract":null,"journal":"Molecular and Cellular Biology","year":2019,"id":47183,"datarank":1.5761838031877762,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":0.9864099582791274,"self_endowment_contribution":0.5897738449086489,"citer_contribution":0.9864099582791274,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":48,"citers_with_citation_signal":41,"citers_with_endowment":41,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":217760,"name":"Margaret A. Strong","orcid":"0000-0002-0055-6573","position":1,"is_corresponding":false},{"id":217761,"name":"John Paul T. Ouyang","orcid":"0000-0003-2030-432X","position":2,"is_corresponding":false},{"id":58180,"name":"Carol W. Greider","orcid":"0000-0002-5494-8126","position":3,"is_corresponding":false},{"id":217759,"name":"Alexandra M. Pike","orcid":"0000-0002-7928-2455","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"TIN2 Functions with TPP1/POT1 To Stimulate Telomerase Processivity","abstract":"TIN2 is an important regulator of telomere length, and mutations in TINF2, the gene encoding TIN2, cause short-telomere syndromes. While the genetics underscore the importance of TIN2, the mechanism through which TIN2 regulates telomere length remains unclear. Here, we tested the effects of human TIN2 on telomerase activity. We identified a new isoform in human cells, TIN2M, that is expressed at levels similar to those of previously studied TIN2 isoforms. All three TIN2 isoforms localized to and maintained telomere integrity in vivo, and localization was not disrupted by telomere syndrome mutations. Using direct telomerase activity assays, we discovered that TIN2 stimulated telomerase processivity in vitro. All of the TIN2 isoforms stimulated telomerase to similar extents. Mutations in the TPP1 TEL patch abrogated this stimulation, suggesting that TIN2 functions with TPP1/POT1 to stimulate telomerase processivity. We conclude from our data and previously published work that TIN2/TPP1/POT1 is a functional shelterin subcomplex.","is_dataset_classified":null,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31383750","pmcid":"PMC6791651","openalex_id":"https://openalex.org/W2965834797","authors":[],"funders":[{"funder_name":"HHS | National Institutes of Health","grant_id":"R37AG009383","title":null},{"funder_name":"HHS | National Institutes of Health","grant_id":"R35CA209974","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM007445","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R37AG009383-20","title":"Structure and Function of Telomerase"},{"funder_name":"National Institutes of Health","grant_id":"5R35CA209974-03","title":"Telomeres and Telomerase in Cancer"},{"funder_name":"National Institutes of Health","grant_id":"5R35CA209974-07","title":"Telomeres and Telomerase in Cancer"}],"total_grants":6,"fwci":3.7495,"citation_percentile":0.94001348,"influential_citations":0,"citation_trend":[{"year":2020,"count":8},{"year":2021,"count":17},{"year":2022,"count":4},{"year":2023,"count":7},{"year":2024,"count":8},{"year":2025,"count":4},{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://www.tandfonline.com/doi/epdf/10.1128/MCB.00593-18?needAccess=true&role=button","host_type":"journal"},{"url":"https://doi.org/10.1128/mcb.00593-18","host_type":"HYBRID"},{"url":"https://www.tandfonline.com/doi/epdf/10.1128/MCB.00593-18?needAccess=true&role=button","host_type":"publisher"},{"url":"https://www.tandfonline.com/doi/pdf/10.1128/MCB.00593-18","host_type":"publisher"},{"url":"https://www.tandfonline.com/doi/full-xml/10.1128/MCB.00593-18","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31383750","host_type":"repository"},{"url":"https://escholarship.org/uc/item/2x86j0vx","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6791651","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6791651","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6791651?pdf=render","host_type":"Europe_PMC"},{"url":"https://mcb.asm.org/content/mcb/39/21/e00593-18.full.pdf","host_type":""},{"url":"http://dx.doi.org/10.1128/MCB.00593-18","host_type":""},{"url":"https://dx.doi.org/10.1128/mcb.00593-18","host_type":""},{"url":"https://escholarship.org/content/qt2x86j0vx/qt2x86j0vx.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1128/mcb.00593-18","host_type":""}],"fields_of_study":["Telomeres, Telomerase, and Senescence","Advanced biosensing and bioanalysis techniques","Medicine","Biology","0301 basic medicine","03 medical and health sciences","0303 health sciences","Aminopeptidases","Cell Line, Tumor","Dipeptidyl-Peptidases and Tripeptidyl-Peptidases","HeLa Cells","Humans","Protein Binding","Protein Isoforms","Serine Proteases","Shelterin Complex","Telomerase","Telomere","Telomere-Binding Proteins"],"mesh_terms":["Shelterin Complex","Aminopeptidases","Dipeptidyl-Peptidases and Tripeptidyl-Peptidases","HeLa Cells","Humans","Protein Binding","Telomere","Telomerase","Protein Isoforms","Telomere-Binding Proteins","Cell Line, Tumor","Serine Proteases","Hela Cells"],"keywords":["Telomere","Telomerase","Biology","Shelterin","Processivity","Gene isoform","Cell biology","Genetics","Molecular biology","Gene","DNA replication","DNA-binding protein","Transcription factor","Alternative splicing","Pot1","Tpp1","Tin2","570","Aging","1.1 Normal biological development and functioning","Telomere-Binding Proteins","610","Medical and Health Sciences","Aminopeptidases","Shelterin Complex","Cell Line","Rare Diseases","Underpinning research","Cell Line, Tumor","Humans","Protein Isoforms","Dipeptidyl-Peptidases and Tripeptidyl-Peptidases","Tumor","Biological Sciences","Hela Cells","Serine Proteases","Developmental Biology","Research Article","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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