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Telomere reverse transcriptase

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https://www.readbyqxmd.com/read/28627628/phosphorothioate%C3%A2-modified-antisense-oligonucleotides-against-human-telomerase-reverse-transcriptase-sensitize-cancer-cells-to-radiotherapy
#1
Fei Cao, Xiaoping Ju, Di Chen, Lingong Jiang, Xiaofei Zhu, Shuiwang Qing, Fang Fang, Yuxin Shen, Zhen Jia, Huojun Zhang
Emergence of resistance, unavoidable systemic toxicity and unsatisfactory efficacy arethe main obstacles for traditional cancer therapy. Combination with phosphorothioate modified antisense oligonucleotides (PS‑ASODN) against human telomerase reverse transcriptase (hTERT) may enhance the therapeutic effect of irradiation. However, the effect of PS‑ASODN against hTERT on the anti‑tumor effects of irradiation in liver cancer remain unclear. In the current study, Walker 256 cells were transfected with hTERT PS‑ASODN...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28587932/preliminary-evidence-that-age-and-sex-affect-exercise-induced-htert-expression
#2
Travis G Cluckey, Nathan C Nieto, Bridger M Rodoni, Tinna Traustadóttir
The ability to repair cellular damage is reduced with aging, resulting in cellular senescence. Telomeres shorten as cells divide but the rate of telomere attrition is modulated by telomerase, an enzyme that adds nucleotides to the chromosome. Shelterin is a protein complex that acts as a negative regulator of telomerase. The aim of the present study was to investigate age-related differences in telomerase and shelterin responses to acute exercise. We hypothesized that acute exercise would stimulate an increased activity of telomerase (measured by telomerase reverse transcriptase, hTERT) without an increase in activity of shelterin (measured by telomeric repeat binding factor 2, TRF2) in both young and older individuals and that hTERT response would be attenuated in older individuals...
June 3, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28580306/enterolactone-reduces-telomerase-activity-and-the-level-of-its-catalytic-subunit-in-breast-cancer-cells
#3
Davod Ilbeigi, Mitra Nourbakhsh, Shahnaz Khaghani, Nahid Einollahi, Nejat Kheiripour, Zafar Gholinejad, Mohammad Alaee, Mostafa Saberian
OBJECTIVE: There is a positive correlation between higher serum phytoestrogen concentrations and lower risk of breast cancer. The activation of telomerase is crucial for the growth of cancer cells; therefore, the aim of this study was to examine the effects of enterolactone (ENL) and enterodiol (END) on this enzyme. MATERIALS AND METHODS: In this experimental study, we performed the viability assay to determine the effects of different concentrations of ENL and END on cell viability, and the effective concentrations of these two compounds on cell growth...
2017: Cell Journal
https://www.readbyqxmd.com/read/28575409/giant-reverse-transcriptase-encoding-transposable-elements-at-telomeres
#4
Irina R Arkhipova, Irina A Yushenova, Fernando Rodriguez
Transposable elements are omnipresent in eukaryotic genomes and have a profound impact on chromosome structure, function and evolution. Their structural and functional diversity is thought to be reasonably well-understood, especially in retroelements, which transpose via an RNA intermediate copied into cDNA by the element-encoded reverse transcriptase, and are characterized by a compact structure. Here we report a novel type of expandable eukaryotic retroelements, which we call Terminons. These elements can attach to G-rich telomeric repeat overhangs at the chromosome ends, in a process apparently facilitated by complementary C-rich repeats at the 3'-end of the RNA template immediately adjacent to a hammerhead ribozyme motif...
May 30, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28572671/interaction-studies-of-carbon-nanomaterials-and-plasma-activated-carbon-nanomaterials-solution-with-telomere-binding-protein
#5
Pankaj Attri, Jitender Gaur, Sooho Choi, Minsup Kim, Rohit Bhatia, Naresh Kumar, Ji Hoon Park, Art E Cho, Eun Ha Choi, Weontae Lee
Most cancer cells have telomerase activity because they can express the human telomerase reverse transcriptase (hTERT) gene. Therefore, the inhibition of the hTERT expression can play an important role in controlling cancer cell proliferation. Our current study aims to inhibit hTERT expression. For this, we synthesized graphene oxide (GO) and a functionalized multiwall carbon nanotube (f-MWCNT), latter treated them with cold atmospheric pressure plasma for further analysis of the hTERT expression. The inhibition of hTERT expression by GO, f-MWCNT, plasma activated GO solution (PGOS), and plasma activated f-MWCNT solution (PCNTS), was studied using two lung cancer cell lines, A549 and H460...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28553482/sensing-telomerase-from-in-vitro-detection-to-in-vivo-imaging
#6
REVIEW
Li-Juan Wang, Fei Ma, Bo Tang, Chun-Yang Zhang
Telomerase is a ribonucleoprotein reverse transcriptase that is responsible for maintaining the telomere length in cells. Telomerase overexpresses in almost all malignant tumor cells, and it has become a promising biomarker and a potential therapy target for cancers. Consequently, accurate and efficient quantification of the telomerase is highly essential to medical diagnostics and therapeutics. Recently, a series of novel telomerase detection methods with excellent performance have been developed, but a overview of in vivo telomerase detection methods is lacking...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28535013/htert-c250t-promoter-mutation-and-telomere-length-as-a-molecular-markers-of-cancer-progression-in-patients-with-head-and-neck-cancer
#7
Wojciech Barczak, Wiktoria M Suchorska, Agnieszka Sobecka, Karolina Bednarowicz, Piotr Machczynski, Pawel Golusinski, Blazej Rubis, Michal M Masternak, Wojciech Golusinski
Squamous cell carcinoma of the head and neck (HNSCC) is the sixth leading cause of cancer worldwide, representing over half a million incidents every year. Cancer cells, including HNSCC, are characterized by increased telomerase activity. This enzymatic complex is active in ~90% of all cancer types and is responsible for the lengthening of telomeres. Highly recurrent point mutations in the human telomerase reverse transcriptase (hTERT) promoter have recently been reported in a number of human neoplasms. The aim of the present study was to analyze the prevalence of the hTERT promoter C250T mutation and telomere length in the blood leukocytes of 61 patients with HNSCC and 49 healthy individuals...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28520570/long-term-exposure-to-mst-312-leads-to-telomerase-reverse-transcriptase-overexpression-in-mcf-7-breast-cancer-cells
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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