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Telomere reverse transcriptase

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https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#1
REVIEW
Julieann Lee, D A Solomon, Tarik Tihan
Genetic profiling is an increasingly useful tool for sub-classification of gliomas in adults and children. Specific gene mutations, structural rearrangements, DNA methylation patterns, and gene expression profiles are now recognized to define molecular subgroups of gliomas that arise in distinct anatomic locations and patient age groups, and also provide a better prediction of clinical outcomes for glioma patients compared to histologic assessment alone. Understanding the role of these distinctive genetic alterations in gliomagenesis is also important for the development of potential targeted therapeutic interventions...
January 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28056029/hcv-induces-telomerase-reverse-transcriptase-increases-its-catalytic-activity-and-promotes-caspase-degradation-in-infected-human-hepatocytes
#2
Zhaowen Zhu, Huy Tran, M Meleah Mathahs, Thomas O Moninger, Warren N Schmidt
INTRODUCTION: Telomerase repairs the telomeric ends of chromosomes and is active in nearly all malignant cells. Hepatitis C virus (HCV) is known to be oncogenic and potential interactions with the telomerase system require further study. We determined the effects of HCV infection on human telomerase reverse transcriptase (TERT) expression and enzyme activity in primary human hepatocytes and continuous cell lines. RESULTS: Primary human hepatocytes and Huh-7.5 hepatoma cells showed early de novo TERT protein expression 2-4 days after infection and these events coincided with increased TERT promoter activation, TERT mRNA, and telomerase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28050263/peculiarities-of-yeasts-and-human-telomerase-rnas-processing
#3
M P Rubtsova, D P Vasilkova, Yu V Naraykina, O A Dontsova
Telomerase is one of the major components of the telomeres -- linear eukaryotic chromosome ends - maintenance system. Linear chromosomes are shortened during each cell division due to the removal of the primer used for DNA replication. Special repeated telomere sequences at the very ends of linear chromosomes prevent the deletion of genome information caused by primer removal. Telomeres are shortened at each replication round until it becomes critically short and is no longer able to protect the chromosome in somatic cells...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28039025/common-variants-of-human-tert-and-terc-genes-and-susceptibility-to-sporadic-alzheimers-disease
#4
D Scarabino, E Broggio, G Gambina, F Pelliccia, R M Corbo
Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD...
December 27, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/28038469/polyunsaturated-fatty-acids-ameliorate-aging-via-redox-telomere-antioncogene-axis
#5
Jingnan Chen, Yan Wei, Xinyu Chen, Jingjing Jiao, Yu Zhang
Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032863/short-term-inhibition-of-tert-induces-telomere-length-independent-cell-cycle-arrest-and-apoptotic-response-in-ebv-immortalized-and-transformed-b-cells
#6
Andrea Celeghin, Silvia Giunco, Riccardo Freguja, Manuela Zangrossi, Silvia Nalio, Riccardo Dolcetti, Anita De Rossi
Besides its canonical role in stabilizing telomeres, telomerase reverse transcriptase (TERT) may promote tumorigenesis through extra-telomeric functions. The possible therapeutic effects of BIBR1532 (BIBR), a powerful TERT inhibitor, have been evaluated in different cellular backgrounds, but no data are currently available regarding Epstein-Barr virus (EBV)-driven B-cell malignancies. Our aim was to characterize the biological effects of TERT inhibition by BIBR on EBV-immortalized lymphoblastoid cell lines (LCLs) and fully transformed Burkitt's lymphoma (BL) cell lines...
December 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/28006764/telomere-dysfunction-in-nonalcoholic-fatty-liver-disease-and-cryptogenic-cirrhosis
#7
Ido Laish, Batya Mannasse-Green, Ruth Hadary, Tal Biron-Shental, Fred M Konikoff, Aliza Amiel, Yona Kitay-Cohen
Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci...
December 23, 2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28002788/tianshengyuan-1-tsy-1-regulates-cellular-telomerase-activity-by-methylation-of-tert-promoter
#8
Weibo Yu, Xiaotian Qin, Yusheng Jin, Yawei Li, Chintda Santiskulvong, Victor Vu, Gang Zeng, Zuofeng Zhang, Michelle Chow, Jianyu Rao
Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27979878/implications-of-telomeres-and-telomerase-in-endometrial-pathology
#9
REVIEW
D K Hapangama, A Kamal, G Saretzki
BACKGROUND: Eukaryotic chromosomal ends are linear and are protected by nucleoprotein complexes known as telomeres. The complex structural anatomy and the diverse functions of telomeres as well as the unique reverse transcriptase enzyme, telomerase that maintains telomeres are under intensive scientific scrutiny. Both are involved in many human diseases including cancer, but also in ageing and chronic disease such as diabetes. Their intricate involvement in many cellular processes and pathways is being dynamically deciphered in many organs including the endometrium...
December 15, 2016: Human Reproduction Update
https://www.readbyqxmd.com/read/27932351/telomerase-reverse-transcriptase-deficiency-prevents-neointima-formation-through-chromatin-silencing-of-e2f1-target-genes
#10
Elizabeth B Endorf, Hua Qing, Jun Aono, Naoto Terami, Geneviève Doyon, Eric Hyzny, Karrie L Jones, Hannes M Findeisen, Dennis Bruemmer
OBJECTIVE: Aberrant proliferation of smooth muscle cells (SMC) in response to injury induces pathological vascular remodeling during atherosclerosis and neointima formation. Telomerase is rate limiting for tissue renewal and cell replication; however, the physiological role of telomerase in vascular diseases remains to be determined. The goal of the present study was to determine whether telomerase reverse transcriptase (TERT) affects proliferative vascular remodeling and to define the molecular mechanism by which TERT supports SMC proliferation...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27900472/tissue-specific-expression-of-telomerase-reverse-transcriptase-gene-variants-in-nicotiana-tabacum
#11
Jana Fišerová Jurečková, Eva Sýkorová, Said Hafidh, David Honys, Jiří Fajkus, Miloslava Fojtová
In tobacco, three sequence variants of the TERT gene have been described. We revealed unbalanced levels of TERT variant transcripts in vegetative tobacco tissues and enhanced TERT transcription and telomerase activity in reproductive tissues. Telomerase is a ribonucleoprotein complex responsible for the maintenance of telomeres, structures delimiting ends of linear eukaryotic chromosomes. In the Nicotiana tabacum (tobacco) allotetraploid plant, three sequence variants (paralogs) of the gene coding for the telomerase reverse transcriptase subunit (TERT) have been described, two of them derived from the maternal N...
November 29, 2016: Planta
https://www.readbyqxmd.com/read/27899638/structure-and-folding-of-the-tetrahymena-telomerase-rna-pseudoknot
#12
Darian D Cash, Juli Feigon
Telomerase maintains telomere length at the ends of linear chromosomes using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). An essential part of TER is the template/pseudoknot domain (t/PK) which includes the template, for adding telomeric repeats, template boundary element (TBE), and pseudoknot, enclosed in a circle by stem 1. The Tetrahymena telomerase holoenzyme catalytic core (p65-TER-TERT) was recently modeled in our 9 Å resolution cryo-electron microscopy map by fitting protein and TER domains, including a solution NMR structure of the Tetrahymena pseudoknot...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895115/shared-subunits-of-tetrahymena-telomerase-holoenzyme-and-replication-protein-a-have-different-functions-in-different-cellular-complexes
#13
Heather E Upton, Henry Chan, Juli Feigon, Kathleen Collins
In most eukaryotes, telomere maintenance relies on telomeric repeat synthesis by a reverse transcriptase named telomerase. To synthesize telomeric repeats, the catalytic subunit telomerase reverse transcriptase (TERT) uses the RNA subunit (TER) as a template. In the ciliate Tetrahymena thermophila, the telomerase holoenzyme consists of TER, TERT, and eight additional proteins, including the telomeric repeat single-stranded DNA-binding protein Teb1 and its heterotrimer partners Teb2 and Teb3. Teb1 is paralogous to the large subunit of the general single-stranded DNA binding heterotrimer replication protein A (RPA)...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27893208/kanahia-laniflora-methanolic-extract-suppressed-proliferation-of-human-non-small-cell-lung-cancer-a549-cells
#14
Mohammad Yahya Alfaifi
Introduction: Lung cancer is one of the most common cancers worldwide. In certain countries such as United States of America, it is the leading cause of related cancer mortality among both men and women. Natural products play an important role in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In this study, we investigated the antiproliferative and apoptotic activities of Kanahia laniflora methanolic extract against human non-small cell lung cancer cells (A549). Methods: Sulforhodamine B colorimetric assays were used to determine the inhibitory effects of a leaf methanolic extract against A549 cells...
1, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27872149/endogenous-tert-n-terminal-tagging-affects-human-telomerase-function-at-telomeres-in-vivo
#15
Kunitoshi Chiba, Jacob M Vogan, Robert A Wu, Manraj S Gill, Xiaozhu Zhang, Kathleen Collins, Dirk Hockemeyer
Telomerase action at telomeres is essential for the immortal phenotype of stem cells and the aberrant proliferative potential of cancer cells. Insufficient telomere maintenance can cause stem cell and tissue failure syndromes, while increased telomerase levels are associated with tumorigenesis. Both pathologies can arise from only small perturbation of telomerase function. To analyze telomerase at its low endogenous expression level, we genetically engineered human pluripotent stem cells (hPSCs) to express various N-terminal fusion proteins of the telomerase reverse transcriptase from its endogenous locus...
November 21, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27856756/global-analysis-of-somatic-structural-genomic-alterations-and-their-impact-on-gene-expression-in-diverse-human-cancers
#16
Babak Alaei-Mahabadi, Joydeep Bhadury, Joakim W Karlsson, Jonas A Nilsson, Erik Larsson
Tumor genomes are mosaics of somatic structural variants (SVs) that may contribute to the activation of oncogenes or inactivation of tumor suppressors, for example, by altering gene copy number amplitude. However, there are multiple other ways in which SVs can modulate transcription, but the general impact of such events on tumor transcriptional output has not been systematically determined. Here we use whole-genome sequencing data to map SVs across 600 tumors and 18 cancers, and investigate the relationship between SVs, copy number alterations (CNAs), and mRNA expression...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27836952/prevalence-and-characteristics-of-tert-and-terc-mutations-in-suspected-genetic-pulmonary-fibrosis
#17
Raphael Borie, Laure Tabèze, Gabriel Thabut, Hilario Nunes, Vincent Cottin, Sylvain Marchand-Adam, Grégoire Prevot, Abdellatif Tazi, Jacques Cadranel, Herve Mal, Lidwine Wemeau-Stervinou, Anne Bergeron Lafaurie, Dominique Israel-Biet, Clement Picard, Martine Reynaud Gaubert, Stephane Jouneau, Jean-Marc Naccache, Julie Mankikian, Christelle Ménard, Jean-François Cordier, Dominique Valeyre, Marion Reocreux, Bernard Grandchamp, Patrick Revy, Caroline Kannengiesser, Bruno Crestani
Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis.We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival...
December 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27821557/telomeres-reproductive-aging-and-genomic-instability-during-early-development
#18
David L Keefe
Implantation rate decreases and miscarriage rate increases with advancing maternal age. The oocyte must be the locus of reproductive aging because donation of oocytes from younger to older women abrogates the effects of aging on fecundity. Nuclear transfer experiments in a mouse model of reproductive aging show that the reproductive aging phenotype segregates with the nucleus rather than the cytoplasm. A number of factors within the nucleus have been hypothesized to mediate reproductive aging, including disruption of cohesions, reduced chiasma, aneuploidy, disrupted meiotic spindles, and DNA damage caused by chronic exposure to reactive oxygen species...
December 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27814571/telomere-protein-complexes-and-their-role-in-lymphoid-malignancies
#19
Julieta Panero, Patricia Dos Santos, Irma Slavutsky
Telomeres are highly regulated and dynamic complexes that protect the genomic DNA and prevent the end of linear chromosomes from being misrecognized as a broken DNA. Due to the end replication problem, telomeres of somatic cells shorten with each cell division, inducing cell senescence. Telomerase is a reverse transcriptase capable of compensating telomere attrition by adding telomere repeats to the ends of chromosomes. Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/27797938/leucocyte-telomere-length-genetic-variants-at-the-tert-gene-region-and-risk-of-pancreatic-cancer
#20
Ying Bao, Jennifer Prescott, Chen Yuan, Mingfeng Zhang, Peter Kraft, Ana Babic, Vicente Morales-Oyarvide, Zhi Rong Qian, Julie E Buring, Barbara B Cochrane, J Michael Gaziano, Edward L Giovannucci, JoAnn E Manson, Kimmie Ng, Shuji Ogino, Thomas E Rohan, Howard D Sesso, Meir J Stampfer, Charles S Fuchs, Immaculata De Vivo, Laufey T Amundadottir, Brian M Wolpin
OBJECTIVE: Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. DESIGN: We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts...
October 21, 2016: Gut
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