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Telomere and telomerase

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https://www.readbyqxmd.com/read/28096444/single-molecule-fret-rosetta-reveals-rna-structural-rearrangements-during-human-telomerase-catalysis
#1
Joseph W Parks, Kalli Kappel, Rhiju Das, Michael D Stone
Maintenance of telomeres by telomerase permits continuous proliferation of rapidly dividing cells, including the majority of human cancers. Despite its direct biomedical significance, the architecture of the human telomerase complex remains unknown. Generating homogeneous telomerase samples has presented a significant barrier to developing improved structural models. Here we pair single-molecule Förster resonance energy transfer (smFRET) measurements with Rosetta modeling to map the conformations of the essential telomerase RNA core domain within the active ribonucleoprotein...
February 2017: RNA
https://www.readbyqxmd.com/read/28092835/effects-of-the-central-potassium-ions-on-the-g-quadruplex-and-stabilizer-binding
#2
Zhiguo Wang, Jun-Ping Liu
Human telomeres undertake the structure of intra-molecular parallel G-quadruplex in the presence of K(+) in eukaryotic cell. Stabilization of the telomere G-quadruplex represents a potential strategy to prevent telomere lengthening by telomerase in cancer therapy. Current work demonstrates that the binding of central K(+) with the parallel G-quadruplex is a coordinated water directed step-wise process. The K(+) above the top G-tetrad is prone to leak into environment and the 5'-adenine quickly flips over the top G-tetrad, leading to the bottom gate of G-tetrads as the only viable pathway of K(+) binding...
January 6, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28076340/telomere-length-assessment-for-prediction-of-organ-transplantation-outcome-future-or-failure-a-review-of-the-literature
#3
Karolina Kłoda, Leszek Domański, Artur Mierzecki
Telomeres are located at each end of eukaryotic chromosomes. Their functional role is genomic stability maintenance. The protective role of telomeres depends on various factors, including number of nucleotides repeats, telomere-binding proteins, and telomerase activity. Organ transplantation is the preferred replacement therapy in the case of chronic kidney disease and the only possibility of sustaining recipients' life in the case of advanced liver failure. While the prevalence of acute rejection is constantly decreasing, prevention of transplanted organ long-term function loss is still challenging...
January 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#4
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
#5
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/28054503/inhibition-of-telomerase-using-bibr1532-enhances-doxorubicin-induced-apoptosis-in-pre-b-acute-lymphoblastic-leukemia-cells
#6
Davood Bashash, Mohadeseh Zareii, Ava Safaroghli-Azar, Mir Davood Omrani, Seyed H Ghaffari
OBJECTIVES: Interest into targeting telomerase in cancer has increased by the recent disclosure that elevated telomerase activity is associated with disease recurrence and poor outcome in cancers. In addition, cellular acquisition of unlimited replicative potential, which is closely related to the maintenance of telomeres mostly via the reactivation of telomerase, has been shown to confer loss of sensitivity to a wide range of anti-neoplastic agents. METHODS: To evaluate whether telomerase inhibition using non-nucleosidic inhibitor of telomerase BIBR1532 could enhance cytotoxic effect of doxorubicin in acute lymphoblastic leukemia, Nalm-6 pre-B ALL cells were subjected to combination treatment and subsequent cell viability, growth kinetics, caspase-3 activity, and transcriptional alteration of p73, p21, FOXO3a, c-Myc, hTERT, and other apoptosis-related target genes were investigated...
January 5, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28050263/peculiarities-of-yeasts-and-human-telomerase-rnas-processing
#7
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
#8
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
#9
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
#10
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/28025427/the-role-of-tert-clptm1l-snps-htert-expression-and-telomere-length-in-the-pathogenesis-of-oral-squamous-cell-carcinoma
#11
Jelena Carkic, Nadja Nikolic, Sanja Radojevic-Skodric, Jovana Kuzmanovic-Pficer, Gavrilo Brajovic, Marija Antunovic, Jelena Milasin, Branka Popovic
The aim of this study was to assess TERT-CLPTM1L single-nucleotide polymorphisms (SNPs) (rs402710 C/T in the CLPTM1L gene; rs2736100 A/C and rs2736098 G/A in the TERT gene) as risk factors for development of oral squamous cell carcinoma (OSCC), and to investigate the relationship between the analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathologic characteristics of OSCC in a Serbian population. Paraffin-embedded tumor samples and buccal swabs from cancer-free controls were genotyped using PCR-RFLP, while tumor RTL values and telomerase expression were estimated by real-time PCR and immunohistochemistry, respectively...
2016: Journal of Oral Science
https://www.readbyqxmd.com/read/28025082/identification-of-g-quadruplex-dna-rna-binders-structure-based-virtual-screening-and-biophysical-characterization
#12
Roberta Rocca, Federica Moraca, Giosuè Costa, Matteo Nadai, Matteo Scalabrin, Carmine Talarico, Simona Distinto, Elias Maccioni, Francesco Ortuso, Anna Artese, Stefano Alcaro, Sara N Richter
BACKGROUND: Recent findings demonstrated that, in mammalian cells, telomere DNA (Tel) is transcribed into telomeric repeat-containing RNA (TERRA), which is involved in fundamental biological processes, thus representing a promising anticancer target. For this reason, the discovery of dual (as well as selective) Tel/TERRA G-quadruplex (G4) binders could represent an innovative strategy to enhance telomerase inhibition. METHODS: Initially, docking simulations of known Tel and TERRA active ligands were performed on the 3D coordinates of bimolecular G4 Tel DNA (Tel2) and TERRA (TERRA2)...
December 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28024882/dha-enriched-fish-oil-upregulates-cyclin-dependent-kinase-inhibitor-2a-p16-ink-expression-and-downregulates-telomerase-activity-without-modulating-effects-of-ppar%C3%AE-pro12ala-polymorphism-in-type-2-diabetic-patients-a-randomized-double-blind-placebo-controlled
#13
Omid Toupchian, Gity Sotoudeh, Anahita Mansoori, Shima Abdollahi, Seyyed Ali Keshavarz, Mahmoud Djalali, Ensieh Nasli-Esfahani, Ehsan Alvandi, Reza Chahardoli, Fariba Koohdani
OBJECTIVE: The present study investigated the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on telomerase activity, mRNA expression of P16(INK), IL-6, and TNF-α considering Pro12Ala polymorphism in the PPARγ gene. METHODS/DESIGN: In this double-blind randomized controlled trial, 72 PPARγ Pro12Ala polymorphism genotyped type 2 diabetic patients aged 30-70 years were randomly assigned to receive 2.4 gr of DHA-enriched fish oil or a placebo for 8 weeks...
December 19, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28009281/peroxiredoxin-1-protects-telomeres-from-oxidative-damage-and-preserves-telomeric-dna-for-extension-by-telomerase
#14
Eric Aeby, Wareed Ahmed, Sophie Redon, Viesturs Simanis, Joachim Lingner
Oxidative damage of telomeres can promote cancer, cardiac failure, and muscular dystrophy. Specific mechanisms protecting telomeres from oxidative damage have not been described. We analyzed telomeric chromatin composition during the cell cycle and show that the antioxidant enzyme peroxiredoxin 1 (PRDX1) is enriched at telomeres during S phase. Deletion of the PRDX1 gene leads to damage of telomeric DNA upon oxidative stress, revealing a protective function of PRDX1 against oxidative damage at telomeres. We also show that the oxidized nucleotide 8-oxo-2'deoxyguanosine-5'-triphosphate (8oxodGTP) causes premature chain termination when incorporated by telomerase and that some DNA substrates terminating in 8oxoG prevent extension by telomerase...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28007578/nmr-based-model-of-human-telomeric-repeat-g-quadruplex-in-complex-with-2-4-6-triarylpyridine-family-ligand
#15
Abdelaziz Kerkour, Jean-Louis Mergny, Gilmar F Salgado
G-quadruplexes (G4) are one of the several different forms of non-canonical DNA structures that can occur in our genome. Their existence is thought to be implicated in important biological functions such as positive and negative transcription regulation or telomeric extension. The human telomeric sequence G4 formed by repetitive nucleotide sequences (T2AG3) at each chromosome end is an important example of intramolecular G4. Knowing the atomic details for different families of ligands targeting G-quadruplex structures hypothetically found in the telomeric repeat it is an important step for rational drug design...
December 19, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28006764/telomere-dysfunction-in-nonalcoholic-fatty-liver-disease-and-cryptogenic-cirrhosis
#16
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/28005428/telomerase-and-the-genetics-of-emphysema-susceptibility-implications-for-pathogenesis-paradigms-and-patient-care
#17
Susan E Stanley, Samantha J Merck, Mary Armanios
In the past five decades, alpha-1 antitrypsin deficiency has been the only known genetic cause of emphysema, yet it explains the genetics in only 1-2% of severe cases. Recently, mutations in telomerase genes were found to induce susceptibility to young-onset, severe, and familial emphysema at a frequency comparable to that of alpha-1 antitrypsin deficiency. Telomerase mutation carriers with emphysema report a family history of idiopathic pulmonary fibrosis, and both lung phenotypes show autosomal dominant inheritance within families...
December 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28002788/tianshengyuan-1-tsy-1-regulates-cellular-telomerase-activity-by-methylation-of-tert-promoter
#18
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/27986801/decreased-telomere-length-in-children-with-cartilage-hair-hypoplasia
#19
Svetlana Kostjukovits, Sofie Degerman, Minna Pekkinen, Paula Klemetti, Mattias Landfors, Göran Roos, Mervi Taskinen, Outi Mäkitie
BACKGROUND: Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia caused by RMRP (RNA component of mitochondrial RNA processing endoribonuclease) gene mutations. Manifestations include short stature, variable immunodeficiency, anaemia and increased risk of malignancies, all of which have been described also in telomere biology disorders. RMRP interacts with the telomerase RT (TERT) subunit, but the influence of RMRP mutations on telomere length is unknown. We measured relative telomere length (RTL) in patients with CHH, their first-degree relatives and healthy controls and correlated RTL with clinical and laboratory features...
December 16, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27979878/implications-of-telomeres-and-telomerase-in-endometrial-pathology
#20
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
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