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Telomere reverse transcriptase

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https://www.readbyqxmd.com/read/28520570/long-term-exposure-to-mst-312-leads-to-telomerase-reverse-transcriptase-overexpression-in-mcf-7-breast-cancer-cells
#1
Karollyne S Morais, Ana Flávia R Guimarãesb, Doralina A R Ramos, Fábio P Silva, Diêgo M de Oliveira
Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. Therefore, antitelomerase therapy is a potentially revolutionary therapeutic strategy, and the antitumor activity of telomerase inhibitors (TI) has been studied extensively recently, mainly for breast cancer. However, the effects expected from treatment with TI will appear only after many cell divisions, but the effects of this long-term approach are unknown. In this work, the consequences of 3120 h exposure of human breast cancer cells to TI MST-312 were investigated...
May 17, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28495680/dna-binding-determinants-and-cellular-thresholds-for-human-telomerase-repeat-addition-processivity
#2
Robert Alexander Wu, Jane Tam, Kathleen Collins
The reverse transcriptase telomerase adds telomeric repeats to chromosome ends. Purified human telomerase catalyzes processive repeat synthesis, which could restore the full ~100 nucleotides of (T2AG3)n lost from replicated chromosome ends as a single elongation event. Processivity inhibition is proposed to be a basis of human disease, but the impacts of different levels of processivity on telomere maintenance have not been examined. Here, we delineate side chains in the telomerase active-site cavity important for repeat addition processivity, determine how they contribute to duplex and single-stranded DNA handling, and test the cellular consequences of partial or complete loss of repeat addition processivity for telomere maintenance...
May 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28487971/azidothymidine-inhibits-cell-growth-and-telomerase-activity-and-induces-dna-damage-in-human-esophageal-cancer
#3
Haoli Wang, Jianwen Zhou, Qiong He, Yu Dong, Yanhui Liu
Esophageal cancer is one of the most common type of malignancies. Telomerase activity, which is absent or weakly detected in the majority of human somatic cells, is elevated in esophageal cancer. Although azidothymidine (AZT), a reverse transcriptase inhibitor, has been utilized as a treatment for tumors, its role in treating esophageal cancer has not been confirmed. The aim of the present study was to determine the effect of AZT on telomerase activity and the proliferation of the human esophageal cancer cell line TE‑11...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28483762/clonal-hematopoiesis-with-and-without-candidate-driver-mutations-is-common-in-the-elderly
#4
Florian Zink, Simon N Stacey, Gudmundur L Norddahl, Michael L Frigge, Olafur T Magnusson, Ingileif Jonsdottir, Thorgeir E Thorgeirsson, Asgeir Sigurdsson, Sigurjon A Gudjonsson, Julius Gudmundsson, Jon G Jonasson, Laufey Tryggvadottir, Thorvaldur Jonsson, Agnar Helgason, Arnaldur Gylfason, Patrick Sulem, Thorunn Rafnar, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Gisli Masson, Augustine Kong, Kari Stefansson
Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells are derived from a single dominant hematopoietic stem cell lineage. Somatic mutations in candidate driver (CD) genes are thought to be responsible for at least some cases of CH. Using whole genome sequencing of 11,262 Icelanders, we found 1,403 cases of CH by using barcodes of mosaic somatic mutations in peripheral blood, irrespective of whether or not they have a mutation in a CD gene. We find that CH is very common in the elderly, trending towards inevitability...
May 8, 2017: Blood
https://www.readbyqxmd.com/read/28479693/telomeres-in-health-and-disease
#5
REVIEW
Shailja Chatterjee
Telomeres are repetitive ribonucleoprotein complexes present at ends of chromosomes. To synthesize this manuscript, a thorough literature search was done using PubMed, MEDLINE and Cochrane review for English-language literature and data available from the period of 2005-2016 were analyzed for manuscript writing. Telomeres help in maintaining the cellular health, inbuilt cellular mechanisms, metabolism and normal cell cycle. Telomerase is a specialized enzyme that possesses catalytic subunits - reverse transcriptase, Terc and dyskerin...
January 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/28471941/basic-science-and-pathogenesis-of-ageing-with-hiv-potential-mechanisms-and-biomarkers
#6
Claire Lagathu, Andrea Cossarizza, Véronique Béréziat, Milena Nasi, Jacqueline Capeau, Marcello Pinti
: The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28469639/telomerase-and-mtor-in-the-brain-the-mitochondria-connection
#7
REVIEW
Satomi Miwa, Gabriele Saretzki
Telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component. Additionally, the protein part TERT (Telomerase Reverse Transcriptase) has various non-canonical functions. For example, it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress, DNA damage and apoptosis. Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28460432/promoter-mutations-and-cellular-distribution-of-telomerase-in-non-clear-cell-and-clear-cell-hepatocellular-carcinoma
#8
Wan Huang, Weiping Zhou, Can Li, Yuan Yang, Yu-Kui Shang, Changsheng Chen, Jing Zhang, Rui Yao, Pei Wang, Wen Wen, Han-Qiang Liu, Ling Wang, Xia Li, Huijie Bian, Zhi-Nan Chen
Reactivation of telomerase is a critical step in the development of hepatocellular carcinoma (HCC). Here we identified the frequency of mutations in telomerase reverse transcriptase (TERT) promoter was 34% in non-clear cell HCC (NCCHCC, n = 259) and 26.3% in clear cell HCC (CCHCC, n = 57). The mutations were independently associated with poor recurrence-free survival of HCCs. Interestingly immunohistochemical analysis demonstrated a higher positive rate of TERT cytoplasmic localization (95%) than nuclear localization (64%) in HCCs...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28441946/the-protein-subunit-of-telomerase-displays-patterns-of-dynamic-evolution-and-conservation-across-different-metazoan-taxa
#9
Alvina G Lai, Natalia Pouchkina-Stantcheva, Alessia Di Donfrancesco, Gerda Kildisiute, Sounak Sahu, A Aziz Aboobaker
BACKGROUND: Most animals employ telomerase, which consists of a catalytic subunit known as the telomerase reverse transcriptase (TERT) and an RNA template, to maintain telomere ends. Given the importance of TERT and telomere biology in core metazoan life history traits, like ageing and the control of somatic cell proliferation, we hypothesised that TERT would have patterns of sequence and regulatory evolution reflecting the diverse life histories across the Animal Kingdom. RESULTS: We performed a complete investigation of the evolutionary history of TERT across animals...
April 26, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28418989/impact-of-antiretroviral-treatment-containing-tenofovir-difumarate-on-the-telomere-length-of-aviremic-hiv-infected-patients
#10
Rocio Montejano, Natalia Stella-Ascariz, Susana Monge, José I Bernardino, Ignacio Pérez-Valero, MaLuisa Montes, Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, Juan González-García, Francisco Arnalich, Jesús Mingorance, Laura Pintado Berniches, Rosario Perona, José R Arribas
OBJECTIVE: To evaluate the in vivo relevance of the inhibitory effect of tenofovir upon telomerase activity observed in vitro. DESIGN: Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) Methods: Telomere length in whole blood was measured by quantitative real time PCR. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders RESULTS:: 200 patients included, 72% male, median age 49 (IQR 45-54...
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28342451/tert-promoter-mutations-in-telomere-biology
#11
REVIEW
Barbara Heidenreich, Rajiv Kumar
Telomere repeats at chromosomal ends, critical to genome integrity, are maintained through an elaborate network of proteins and pathways. Shelterin complex proteins shield telomeres from induction of DNA damage response to overcome end protection problem. A specialized ribonucleic protein, telomerase, maintains telomere homeostasis through repeat addition to counter intrinsic shortcomings of DNA replication that leads to gradual sequence shortening in successive mitoses. The biogenesis and recruitment of telomerase composed of telomerase reverse transcriptase (TERT) subunit and an RNA component, takes place through the intricate machinery that involves an elaborate number of molecules...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28324508/in-vitro-preparation-and-crystallization-of-vertebrate-telomerase-subunits
#12
Jing Huang, Christopher J Bley, Dustin P Rand, Julian J L Chen, Ming Lei
Telomerase is a unique reverse transcriptase that replicates the telomeric DNA at most eukaryotic chromosomal ends. The telomerase consists of the catalytic protein subunit TERT and the RNA component TR that provides the template for telomeric DNA synthesis. In vitro reconstitution of telomerase core components in large quantity is the prerequisite to studying the catalytic mechanisms of telomerase at the structural level; however, large-scale preparation of recombinant telomerase, especially that of higher eukaryotes, has been a big challenge for a long time...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324503/visualization-of-human-telomerase-localization-by-fluorescence-microscopy-techniques
#13
Eladio Abreu, Rebecca M Terns, Michael P Terns
Human telomerase is a ribonucleoprotein (RNP) that synthesizes DNA repeats at the ends of chromosomes and maintains telomere length and genome stability. The enzyme is comprised of telomerase RNA (hTR) (which provides the template for telomere addition) and several protein subunits including telomerase reverse transcriptase (hTERT) (the catalytic component). Intracellular trafficking of the enzyme has emerged as an important factor in the regulation of telomerase activity. Telomerase trafficking between nuclear Cajal bodies (proposed sites of telomerase biogenesis and regulation) and telomeres (sites of action) is regulated by the cell cycle in concordance with telomere synthesis during S phase...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324500/analysis-of-yeast-telomerase-by-primer-extension-assays
#14
Min Hsu, Neal F Lue
Telomeres are specialized nucleoprotein structures located at eukaryotic chromosomal termini, which are required for chromosome stability and are maintained by a reverse transcriptase named telomerase. Budding yeast has served as an extremely useful model system for analyzing telomere maintenance because the organism offers a wide range of genetic and biochemical tools. Several milestones in telomerase research have been reached through investigation of the yeast system. For example, the consequence of telomerase loss was first characterized in the budding yeast Saccharomyces cerevisiae...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28320284/apoptotic-endonuclease-endog-inhibits-telomerase-activity-and-induces-malignant-transformation-of-human-cd4-t-cells
#15
D A Vasina, D D Zhdanov, E V Orlova, V S Orlova, M V Pokrovskaya, S S Aleksandrova, N N Sokolov
Telomerase activity is regulated by an alternative splicing of mRNA of the telomerase catalytic subunit hTERT (human telomerase reverse transcriptase). Increased expression of the inactive spliced hTERT results in inhibition of telomerase activity. Little is known about the mechanism of hTERT mRNA alternative splicing. This study was aimed at determining the effect of an apoptotic endonuclease G (EndoG) on alternative splicing of hTERT and telomerase activity in CD4+ human T lymphocytes. Overexpression of EndoG in CD4+ T cells downregulated the expression of the active full-length hTERT variant and upregulated the inactive alternatively spliced variant...
January 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28301767/progress-in-human-and-tetrahymena-telomerase-structure
#16
Henry Chan, Yaqiang Wang, Juli Feigon
Telomerase is an RNA-protein complex that extends the 3' ends of linear chromosomes, using a unique telomerase reverse transcriptase (TERT) and template in the telomerase RNA (TR), thereby helping to maintain genome integrity. TR assembles with TERT and species-specific proteins, and telomerase function in vivo requires interaction with telomere-associated proteins. Over the past two decades, structures of domains of TR and TERT as well as other telomerase- and telomere-interacting proteins have provided insights into telomerase function...
March 15, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28300824/association-between-the-telomerase-rs2736098_tt-genotype-and-a-lower-risk-of-chronic-hepatitis-b-and-cirrhosis-in-chinese-males
#17
Guanghui Cheng, Xiaotian Yuan, Fang Wang, Qing Sun, Qian Xin, Kailin Li, Chao Sun, Zhaomin Lin, Yun Luan, Yiteng Xu, Ping Li, Feng Kong, Dawei Xu
OBJECTIVES: Chronic hepatitis B (CHB) is caused by infection of hepatitis B virus (HBV) and liver cirrhosis (LC) is its most common complication. The accumulated evidence indicates a genetic context of HBV infection phenotypes. Here we determine a potential association of CHB/LC with the genetic variant of telomerase reverse transcriptase (TERT), a key player in aging including immune-senescence. METHODS: The study included 227 Chinese CHB patients and 315 sex/age-matched healthy controls...
March 16, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28289249/control-of-cellular-aging-tissue-function-and-cancer-by-p53-downstream-of-telomeres
#18
Caitlin M Roake, Steven E Artandi
Telomeres, the nucleoprotein complex at the ends of eukaryotic chromosomes, perform an essential cellular role in part by preventing the chromosomal end from initiating a DNA-damage response. This function of telomeres can be compromised as telomeres erode either as a consequence of cell division in culture or as a normal part of cellular ageing in proliferative tissues. Telomere dysfunction in this context leads to DNA-damage signaling and activation of the tumor-suppressor protein p53, which then can prompt either cellular senescence or apoptosis...
March 13, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28281877/comprehensive-analysis-of-interaction-networks-of-telomerase-reverse-transcriptase-with-multiple-bioinformatic-approaches-deep-mining-the-potential-functions-of-telomere-and-telomerase
#19
Chunyu Hou, Fei Wang, Xuewen Liu, Guangming Chang, Feng Wang, Xin Geng
Telomerase reverse transcriptase (TERT) is the protein component of telomerase complex. Evidence has accumulated showing that the nontelomeric functions of TERT are independent of telomere elongation. However, the mechanisms governing the interaction between TERT and its target genes are not revealed clear. The biological functions of TERT are not fully elucidated and have thus far been underestimated. To further explore these functions, we investigated TERT interaction networks using multiple bioinformatic databases, including BioGRID, STRING, DAVID, GeneCards, GeneMANIA, PANTHER, miRWalk, mirTarBase, miRNet, miRDB, and TargetScan...
April 21, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28271343/new-molecular-considerations-for-glioma-idh-atrx-braf-tert-h3-k27m
#20
REVIEW
Michael Karsy, Jian Guan, Adam L Cohen, Randy L Jensen, Howard Colman
PURPOSE OF REVIEW: This review will discuss the role of several key players in glioma classification and biology, namely isocitrate dehydrogenase 1 and 2 (IDH1/2), alpha thalassemia/mental retardation syndrome X-linked (ATRX), B-Raf (BRAF), telomerase reverse transcriptase (TERT), and H3K27M. RECENT FINDINGS: IDH1/2 mutation delineates oligoden-droglioma, astrocytoma, and secondary glioblastoma (GBM) from primary GBM and lower-grade gliomas with biology similar to GBM...
February 2017: Current Neurology and Neuroscience Reports
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