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Telomere and telomerase

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https://www.readbyqxmd.com/read/28716051/mir-380-5p-mediated-repression-of-tep1-and-tspyl5-interferes-with-telomerase-activity-and-favours-the-emergence-of-an-alt-like-phenotype-in-diffuse-malignant-peritoneal-mesothelioma-cells
#1
Graziella Cimino-Reale, Paolo Gandellini, Francesca Santambrogio, Marta Recagni, Nadia Zaffaroni, Marco Folini
BACKGROUND: Understanding the molecular/cellular underpinnings of diffuse malignant peritoneal mesothelioma (DMPM), a fatal malignancy with limited therapeutic options, is of utmost importance for the fruitful management of the disease. In this context, we previously found that telomerase activity (TA), which accounts for the limitless proliferative potential of cancer cells, is prognostic for disease relapse and cancer-related death in DMPM patients. Consequently, the identification of factors involved in telomerase activation/regulation may pave the way towards the development of novel therapeutic interventions for the disease...
July 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28710328/de-novo-telomere-addition-at-chromosome-breaks-dangerous-liaisons
#2
Dmitri Churikov, Vincent Géli
Telomerase counteracts the loss of terminal DNA sequences from chromosome ends; however, it may erroneously add telomeric repeats to DNA double-strand breaks. In this issue, Ouenzar et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610071) uncover cell cycle-dependent sequestration of the telomerase RNA in nucleoli, a process that excludes telomerase from DNA repair sites.
July 14, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28705647/telomerase-activity-in-patients-with-stage-2-5d-chronic-kidney-disease
#3
Veysel Kidir, Ayse Aynali, Atila Altuntas, Salih Inal, Buket Aridogan, Mehmet Tugrul Sezer
BACKGROUND: Molecular mechanisms of increased cardiovascular mortality in chronic kidney disease (CKD) associated with biological age are not well understood. Recent studies support the hypothesis that common factors responsible for this phenomenon are cellular aging and telomere dysfunction. OBJECTIVES: The purpose of this study was to investigate the relation between telomerase activity and CKD stages. METHODS: The study included 120 patients who were followed-up for CKD stage 2-5D, composed of 30 patients of each stage and 30 healthy volunteers without any known disease who were admitted to our hospital for routine check-ups...
July 10, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28704482/proteomic-identification-of-proteins-differentially-expressed-following-overexpression-of-htert-human-telomerase-reverse-transcriptase-in-cancer-cells
#4
Rishi Kumar Jaiswal, Pramod Kumar, Amod Sharma, Deepak Kumar Mishra, Pramod Kumar Yadava
Reverse transcriptase activity of telomerase adds telomeric repeat sequences at extreme ends of the newly replicated chromosome in actively dividing cells. Telomerase expression is not detected in terminally differentiated cells but is noticeable in 90% of the cancer cells. hTERT (human telomerase reverse transcriptase) expression seems to promote invasiveness of cancer cells. We here present proteomic profiles of cells overexpressing or knocked down for hTERT. This study also attempts to find out the potential interacting partners of hTERT in cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28700353/chiral-platinum-ii-4-2-3-dihydroxypropyl-formamide-oxo-aporphine-foa-complexes-promote-tumor-cells-apoptosis-by-directly-targeting-g-quadruplex-dna-in-vitro-and-in-vivo
#5
Qi-Pin Qin, Jiao-Lan Qin, Ming Chen, Yu-Lan Li, Ting Meng, Jie Zhou, Hong Liang, Zhen-Feng Chen
Three platinum(II) complexes, 4 (LC-004), 5 (LC-005), and 6 (LC-006), with the chiral FOA ligands R/S-(±)-FOA (1), R-(+)-FOA (2) and S-(-)-FOA (3), respectively, were synthesized and characterized. As potential anti-tumor agents, these complexes show higher cytotoxicity to BEL-7404 cells than the HL-7702 normal cells. They are potential telomerase inhibitors that target c-myc and human telomeric G-quadruplex DNA. Compared to complexes 4 and 5, 6 exhibited higher binding affinities towards telomeric, c-myc G-quadruplex DNA and caspase-3/9, thereby inducing senescence and apoptosis to a greater extent in tumor cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700015/telomere-length-and-htert-in-mania-and-subsequent-remission
#6
Rugül Köse Çinar
Objective: The findings of telomere length (TL) studies in bipolar disorder (BD) are controversial. The aim of the present study was to detect TL, human telomerase reverse transcriptase (hTERT), and brain derived neurotrophic factor (BDNF) in severe mania and subsequent remission. Methods: Twenty-one medication-free male patients and 20 age and gender matched controls were recruited. The patients were followed in the inpatient clinic, and comparisons were made between the same patients in their remission state and controls...
July 6, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28697848/roles-of-rnase-p-and-its-subunits
#7
REVIEW
Nayef Jarrous
Recent studies show that nuclear RNase P is linked to chromatin structure and function. Thus, variants of this ribonucleoprotein (RNP) complex bind to chromatin of small noncoding RNA genes; integrate into initiation complexes of RNA polymerase (Pol) III; repress histone H3.3 nucleosome deposition; control tRNA and PIWI-interacting RNA (piRNA) gene clusters for genome defense; and respond to Werner syndrome helicase (WRN)-related replication stress and DNA double-strand breaks (DSBs). Likewise, the related RNase MRP and RMRP-TERT (telomerase reverse transcriptase) are implicated in RNA-dependent RNA polymerization for chromatin silencing, whereas the telomerase carries out RNA-dependent DNA polymerization for telomere lengthening...
July 8, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28688962/stress-cell-senescence-and-organismal-ageing
#8
REVIEW
João Pedro de Magalhães, João F Passos
Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely accepted that senescence plays a role in vivo. An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing...
July 5, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28677643/telomeres-and-telomerase-role-in-marek-s-disease-virus-pathogenesis-integration-and-tumorigenesis
#9
REVIEW
Ahmed Kheimar, Renato L Previdelli, Darren J Wight, Benedikt B Kaufer
Telomeres protect the ends of vertebrate chromosomes from deterioration and consist of tandem nucleotide repeats (TTAGGG)n that are associated with a number of proteins. Shortening of the telomeres occurs during genome replication, thereby limiting the replication potential of somatic cells. To counteract this shortening, vertebrates encode the telomerase complex that maintains telomere length in certain cell types via de novo addition of telomeric repeats. Several herpesviruses, including the highly oncogenic alphaherpesvirus Marek's disease virus (MDV), harbor telomeric repeats (TMR) identical to the host telomere sequences at the ends of their linear genomes...
July 4, 2017: Viruses
https://www.readbyqxmd.com/read/28677271/telomerase-reverse-transcriptase-germline-mutations-and-hepatocellular-carcinoma-in-patients-with-nonalcoholic-fatty-liver-disease
#10
Benedetta Donati, Alessandro Pietrelli, Piero Pingitore, Paola Dongiovanni, Andrea Caddeo, Lucy Walker, Guido Baselli, Serena Pelusi, Chiara Rosso, Ester Vanni, Ann Daly, Rosellina Margherita Mancina, Antonio Grieco, Luca Miele, Stefania Grimaudo, Antonio Craxi, Salvatore Petta, Laura De Luca, Silvia Maier, Giorgio Soardo, Elisabetta Bugianesi, Fabio Colli, Renato Romagnoli, Quentin M Anstee, Helen L Reeves, Anna Ludovica Fracanzani, Silvia Fargion, Stefano Romeo, Luca Valenti
In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced...
July 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28675175/telomeres-and-telomerase-in-prostate-cancer-development-and-therapy
#11
REVIEW
Mindy Kim Graham, Alan Meeker
Aberrations in telomere biology are among the earliest events in prostate cancer tumorigenesis and continue during tumour progression. Substantial telomere shortening occurs in prostate cancer cells and high-grade prostatic intraepithelial neoplasia. Not all mechanisms of telomere shortening are understood, but oxidative stress from local inflammation might accelerate prostatic telomere loss. Critically short telomeres can drive the accumulation of tumour-promoting genomic alterations; however, continued telomere erosion is unsustainable and must be mitigated to ensure cancer cell survival and unlimited replication potential...
July 4, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28672148/perfluorinated-substances-and-telomeres-in-an-arctic-seabird-cross-sectional-and-longitudinal-approaches
#12
Pierre Blévin, Frédéric Angelier, Sabrina Tartu, Paco Bustamante, Dorte Herzke, Børge Moe, Claus Bech, Geir Wing Gabrielsen, Jan Ove Bustnes, Olivier Chastel
Telomeres are non-coding DNA repeats located at the termini of eukaryotic chromosomes, regulated by dynamic processes balancing shortening and maintenance. Despite a mechanism to slow-down telomere shortening, cell division leads to progressive attrition of chromosomes, leading to the onset of cellular senescence or apoptosis. However, telomere restoration based on telomerase activity is the primary mechanism for telomere maintenance. Telomere length is associated to health and survival and can be impacted by a broad panel of environmental factors...
June 30, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28667246/genetic-profile-and-biological-implication-of-pin2-trf1-interacting-telomerase-inhibitor-1-pinx1-in-human-cancers-an-analysis-using-the-cancer-genome-atlas
#13
Wei-Juan Huang, Mei Li, Xiao-Han Jin, Xiao-Jia Huang, Wei Zhao, Xiao-Peng Tian
Pin2/TRF1-interacting telomere inhibitor 1 (PinX1) was originally identified as a telomerase inhibitor, involved in maintaining telomerase activity, telomere length, and chromosomal stability. However, research has shown that PinX1 can have opposing molecular status in its expression patterns in several other tumor types. We thus investigated the genetic profile and biological implication of PinX1 in several human cancers using the cBioportal database. Our results showed that PinX1 deletion accounted for the most alterations, with the frequency of its deletion regularly occurring in pathological types of carcinosarcoma and adenocarcinoma...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28666128/terra-rna-antagonizes-atrx-and-protects-telomeres
#14
Hsueh-Ping Chu, Catherine Cifuentes-Rojas, Barry Kesner, Eric Aeby, Hun-Goo Lee, Chunyao Wei, Hyun Jung Oh, Myriam Boukhali, Wilhelm Haas, Jeannie T Lee
Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28666126/telomere-length-determines-terra-and-r-loop-regulation-through-the-cell-cycle
#15
Marco Graf, Diego Bonetti, Arianna Lockhart, Kamar Serhal, Vanessa Kellner, André Maicher, Pascale Jolivet, Maria Teresa Teixeira, Brian Luke
Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28666010/dysregulation-of-h-aca-ribonucleoprotein-components-in-chronic-lymphocytic-leukemia
#16
Patricia Carolina Dos Santos, Julieta Panero, Carmen Stanganelli, Virginia Palau Nagore, Flavia Stella, Raimundo Bezares, Irma Slavutsky
Telomeres are protective repeats of TTAGGG sequences located at the end of human chromosomes. They are essential to maintain chromosomal integrity and genome stability. Telomerase is a ribonucleoprotein complex containing an internal RNA template (hTR) and a catalytic subunit (hTERT). The human hTR gene consists of three major domains; among them the H/ACA domain is essential for telomere biogenesis. H/ACA ribonucleoprotein (RNP) complex is composed of four evolutionary conserved proteins, including dyskerin (encoded by DKC1 gene), NOP10, NHP2 and GAR1...
2017: PloS One
https://www.readbyqxmd.com/read/28665427/effects-of-bioactive-compounds-on-senescence-and-components-of-senescence-associated-secretory-phenotypes-in-vitro
#17
REVIEW
Janubová Mária, Žitňanová Ingrid
Senescence is a permanent cell cycle arrest that is accompanied by changes in cell morphology and physiology occurring in vitro and in vivo. Senescence evolved as a beneficial response to damage promoting wound healing, limiting fibrosis, fighting against cancer and helping embryonic development. However, excessive accumulation of senescent cells is considered to play a substantial role in the development of aging-related diseases and other morphological and physiological changes associated with aging. Therefore, the aim of many researchers is to find out a way to eliminate senescent cells and improve the health condition of aging people...
June 30, 2017: Food & Function
https://www.readbyqxmd.com/read/28659816/cardioprotective-effects-of-sirt6-in-a-mouse-model-of-transverse-aortic-constriction-induced-heart-failure
#18
Yongming Li, Xianda Meng, Wenguang Wang, Fu Liu, Zhiru Hao, Yang Yang, Jinbo Zhao, Wensi Yin, Lijuan Xu, Ruiping Zhao, Jiang Hu
SIRT6, a member of the NAD (+)-dependent class III deacetylase sirtuin family, plays important roles in the maintenance of cardiovascular homeostasis. Telomere shortening is a risk factor for age-associated diseases, including heart disease. In the present study, we investigated the role of SIRT6 and telomerase in a mouse model of transverse aortic constriction (TAC)-induced heart failure. SIRT6, telomerase reverse transcriptase (TERT), and telomere repeat binding factor (TRF)-1 were significantly downregulated in TAC mice compared with their expression in sham-operated mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28659185/the-genome-wide-transcription-response-to-telomerase-deficiency-in-the-thermotolerant-yeast-hansenula-polymorpha-dl-1
#19
Alexey V Beletsky, Alexander N Malyavko, Maria V Sukhanova, Eugenia S Mardanova, Maria I Zvereva, Olga A Petrova, Yulia Yu Parfenova, Maria P Rubtsova, Andrey V Mardanov, Olga I Lavrik, Olga A Dontsova, Nikolai V Ravin
BACKGROUND: In the course of replication of eukaryotic chromosomes, the telomere length is maintained due to activity of telomerase, the ribonucleoprotein reverse transcriptase. Abolishing telomerase function causes progressive shortening of telomeres and, ultimately, cell cycle arrest and replicative senescence. To better understand the cellular response to telomerase deficiency, we performed a transcriptomic study for the thermotolerant methylotrophic yeast Hansenula polymorpha DL-1 lacking telomerase activity...
June 28, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28656847/the-telomere-effect-a-revolutionary-approach-to-living-younger-healthier-longer-blackburn-elizabeth-and-epel-elissa-the-telomere-effect-a-revolutionary-approach-to-living-younger-healthier-longer-417pp-%C3%A2-14-99-orion-books-9780297609230-0297609238-formula-see
#20
(no author information available yet)
Elizabeth Blackburn received a Nobel prize for discovering the molecular nature of telomeres (the ends of our chromosomes that serve as protective caps) and telomerase (the enzyme that maintains telomeres).
June 28, 2017: Nursing Standard
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