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VSGs are monoallelically expressed from subtelomeric loci, and telomere proteins regulate VSG monoallelic expression and VSG switching. T. brucei telomerase is essential for telomere maintenance, but no regulators of telomerase have been identified. T. brucei appears to lack OB fold-containing telomere-specific ssDNA binding factors that are critical for coordinating telomere G- and C-strand syntheses in higher eukaryotes. We identify POLIE as a telomere protein essential for telomere integrity. POLIE-depleted cells have more frequent VSG gene conversion-mediated VSG switching and an increased amount of telomeric circles (T-circles), indicating that POLIE suppresses DNA recombination at the telomere\/subtelomere. POLIE-depletion elongates telomere 3\u2032 overhangs dramatically, indicating that POLIE is essential for coordinating DNA syntheses of the two telomere strands. POLIE depletion increases the level of telomerase-dependent telomere G-strand extension, identifying POLIE as the first T. brucei telomere protein that suppresses telomerase. Furthermore, depletion of POLIE results in an elevated telomeric C-circle level, suggesting that the telomere C-strand experiences replication stress and that POLIE may promote telomere C-strand synthesis. Therefore, T. brucei uses a novel mechanism to coordinate the telomere G- and C-strand DNA syntheses.<\/jats:p>","DOI":"10.1093\/nar\/gkac023","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T15:10:44Z","timestamp":1641568244000},"page":"2036-2050","source":"Crossref","is-referenced-by-count":9,"title":["POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4885-5676","authenticated-orcid":false,"given":"M A G","family":"Rabbani","sequence":"first","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko Luis","family":"Tonini","sequence":"additional","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjia","family":"Afrin","sequence":"additional","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-9876","authenticated-orcid":false,"given":"Bibo","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA"},{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland\u00a0OH 44195, USA"},{"name":"Center for RNA Science and Therapeutics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"2022022611405094400_B1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41580-021-00328-y","article-title":"Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization","volume":"22","author":"Lim","year":"2021","journal-title":"Nat. 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