دورية أكاديمية
أعرض في EDS

POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes.

التفاصيل البيبلوغرافية
العنوان: POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes.
المؤلفون: Rabbani MAG; 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., Tonini ML; 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., Afrin M; 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., Li B; 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.; Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland OH 44195, USA.; Center for RNA Science and Therapeutics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
المصدر: Nucleic acids research [Nucleic Acids Res] 2022 Feb 28; Vol. 50 (4), pp. 2036-2050.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Telomerase*/genetics , Telomerase*/metabolism , Telomere*/genetics , Telomere*/metabolism, Trypanosoma/*metabolism, DNA/metabolism ; Humans ; Trypanosoma/genetics ; Variant Surface Glycoproteins, Trypanosoma/genetics
مستخلص: Trypanosoma brucei causes human African trypanosomiasis and sequentially expresses distinct VSGs, its major surface antigen, to achieve host immune evasion. 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' 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.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: R01 AI127562 United States AI NIAID NIH HHS; S10 OD025252 United States OD NIH HHS
المشرفين على المادة: 0 (Variant Surface Glycoproteins, Trypanosoma)
9007-49-2 (DNA)
EC 2.7.7.49 (Telomerase)
تواريخ الأحداث: Date Created: 20220121 Date Completed: 20220415 Latest Revision: 20230908
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8887473
DOI: 10.1093/nar/gkac023
PMID: 35061898
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkac023