{"doi":"10.1101/gad.1881810","title":"Functional interaction between telomere protein TPP1 and telomerase","abstract":"<jats:p>Human chromosome end-capping and telomerase regulation require POT1 (Protection of Telomeres 1) and TPP1 proteins, which bind to the 3′ ssDNA extension of human telomeres. POT1–TPP1 binding to telomeric DNA activates telomerase repeat addition processivity. We now provide evidence that this POT1–TPP1 activation requires specific interactions with telomerase, rather than it being a DNA substrate-specific effect. First, telomerase from the fish medaka, which extends the same telomeric DNA primer as human telomerase, was not activated by human POT1–TPP1. Second, mutation of a conserved glycine, Gly100 in the TEN (telomerase essential N-terminal) domain of TERT, abolished the enhancement of telomerase processivity by POT1–TPP1, in contrast to other single amino acid mutations. Chimeric human–fish telomerases that contained the human TEN domain were active but not stimulated by POT1–TPP1, showing that additional determinants of processivity lie outside the TEN domain. Finally, primers bound to mouse POT1A and human TPP1 were activated for extension by human telomerase, whereas mPOT1A–mTPP1 was most active with mouse telomerase, indicating that these mammalian telomerases have specificity for their respective TPP1 proteins. We suggest that a sequence-specific interaction between TPP1 in the TPP1–POT1–telomeric DNA complex and the G100 region of the TEN domain of TERT is necessary for high-processivity telomerase action.</jats:p>","journal":"Genes &amp; Development","year":2010,"id":47333,"datarank":4.521429766944234,"base_score":4.875197323201151,"endowment":4.875197323201151,"self_citation_contribution":0.7312795984801728,"citation_network_contribution":3.7901501684640606,"self_endowment_contribution":0.7312795984801728,"citer_contribution":3.7901501684640606,"corpus_percentile":null,"corpus_rank":null,"citation_count":130,"citer_count":115,"citers_with_citation_signal":95,"citers_with_endowment":95,"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":218798,"name":"Elaine R. Podell","orcid":null,"position":1,"is_corresponding":false},{"id":218799,"name":"Jayakrishnan Nandakumar","orcid":null,"position":2,"is_corresponding":false},{"id":218800,"name":"Thomas R. Cech","orcid":null,"position":3,"is_corresponding":false},{"id":218797,"name":"Arthur J. Zaug","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Functional interaction between telomere protein TPP1 and telomerase","abstract":"<jats:p>Human chromosome end-capping and telomerase regulation require POT1 (Protection of Telomeres 1) and TPP1 proteins, which bind to the 3′ ssDNA extension of human telomeres. POT1–TPP1 binding to telomeric DNA activates telomerase repeat addition processivity. We now provide evidence that this POT1–TPP1 activation requires specific interactions with telomerase, rather than it being a DNA substrate-specific effect. First, telomerase from the fish medaka, which extends the same telomeric DNA primer as human telomerase, was not activated by human POT1–TPP1. Second, mutation of a conserved glycine, Gly100 in the TEN (telomerase essential N-terminal) domain of TERT, abolished the enhancement of telomerase processivity by POT1–TPP1, in contrast to other single amino acid mutations. Chimeric human–fish telomerases that contained the human TEN domain were active but not stimulated by POT1–TPP1, showing that additional determinants of processivity lie outside the TEN domain. Finally, primers bound to mouse POT1A and human TPP1 were activated for extension by human telomerase, whereas mPOT1A–mTPP1 was most active with mouse telomerase, indicating that these mammalian telomerases have specificity for their respective TPP1 proteins. We suggest that a sequence-specific interaction between TPP1 in the TPP1–POT1–telomeric DNA complex and the G100 region of the TEN domain of TERT is necessary for high-processivity telomerase action.</jats:p>","is_dataset_classified":null,"base_score":4.875197323201151,"endowment":4.875197323201151,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20231318","pmcid":"PMC2841338","openalex_id":"https://openalex.org/W2055707604","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":10,"citation_trend":[{"year":2012,"count":15},{"year":2013,"count":13},{"year":2014,"count":16},{"year":2015,"count":6},{"year":2016,"count":5},{"year":2017,"count":5},{"year":2018,"count":10},{"year":2019,"count":7},{"year":2020,"count":8},{"year":2021,"count":5},{"year":2022,"count":4},{"year":2023,"count":7},{"year":2024,"count":3},{"year":2025,"count":3},{"year":2026,"count":2}],"oa_status":"gold","license":null,"oa_locations":[{"url":"http://genesdev.cshlp.org/content/24/6/613.full.pdf","host_type":"journal"},{"url":"http://genesdev.cshlp.org/content/24/6/613.full.pdf","host_type":"GOLD"},{"url":"http://genesdev.cshlp.org/content/24/6/613.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/gad.1881810","host_type":"publisher"},{"url":"https://doi.org/10.1101/gad.1881810","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20231318","host_type":"repository"},{"url":"https://scholar.colorado.edu/concern/articles/ns064660f","host_type":"repository"},{"url":"https://scholar.colorado.edu/chem_facpapers/21","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2841338","host_type":"repository"}],"fields_of_study":["Telomeres, Telomerase, and Senescence","Mitochondrial Function and Pathology","RNA Interference and Gene Delivery","Biology","Medicine","Animals","Cell Line","Enzyme Activation","Humans","Mice","Models, Molecular","Mutation","Oryzias","Protein Structure, Tertiary","Recombinant Fusion Proteins","Shelterin Complex","Telomerase","Telomere-Binding Proteins"],"mesh_terms":["Shelterin Complex","Animals","Cell Line","Enzyme Activation","Humans","Models, Molecular","Mutation","Oryzias","Recombinant Fusion Proteins","Protein Structure, Tertiary","Telomerase","Telomere-Binding Proteins","Mice"],"keywords":["Biology","Telomere","Telomerase","Telomere-binding protein","Genetics","DNA-binding protein","Molecular biology","Cell biology","Cancer research","DNA","Gene","Transcription factor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-18T15:40:43.613830Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}