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Telomere reverse transcriptase

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https://www.readbyqxmd.com/read/28324508/in-vitro-preparation-and-crystallization-of-vertebrate-telomerase-subunits
#1
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
#2
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
#3
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/28301767/progress-in-human-and-tetrahymena-telomerase-structure
#4
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
#5
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
#6
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-approach-deep-mining-the-potential-functions-of-telomere-and-telomerase
#7
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 non-telomeric 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...
March 6, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28271343/new-molecular-considerations-for-glioma-idh-atrx-braf-tert-h3-k27m
#8
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
https://www.readbyqxmd.com/read/28264499/current-insights-to-regulation-and-role-of-telomerase-in-human-diseases
#9
REVIEW
Mert Burak Ozturk, Yinghui Li, Vinay Tergaonkar
The telomerase ribonucleoprotein complex has a pivotal role in regulating the proliferation and senescence of normal somatic cells as well as cancer cells. This complex is comprised mainly of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) and other associated proteins that function to elongate telomeres localized at the end of the chromosomes. While reactivation of telomerase is a major hallmark of most cancers, together with the synergistic activation of other oncogenic signals, deficiency in telomerase and telomeric proteins might lead to aging and senescence-associated disorders...
February 28, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28251947/-cisplatin-induced-apoptotic-endonuclease-endog-inhibits-telomerase-activity-and-causes-malignant-transformation-of-human-cd4-t-lymphocytes
#10
D D Zhdanov, D А Vasina, E V Orlova, V S Orlova, V S Pokrovsky, M V Pokrovskaya, S S Aleksandrova, N N Sokolov
Alternative splicing of telomerase catalytic subunit hTERT pre-mRNA (human Telomerase Reverse Transcriptase) regulates telomerase activity. Increased expression of non-active splice variant hTERT results in inhibition of telomerase. Apoptotic endonuclease EndoG is known to participate in hTERT alternative splicing. Expression of EndoG can be induced in response to DNA damages. The aim of this study was to determine the ability of a DNA-damaging compound, cisplatin, to induce EndoG and its influence on alternative splicing of hTERT and telomerase activity in human CD4+ Т lymphocytes...
January 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28251405/differential-decrease-in-soluble-and-dna-bound-telomerase-in-senescent-human-fibroblasts
#11
Snir Yehuda, Hagai Yanai, Esther Priel, Vadim E Fraifeld
The role of telomere shortening in the induction of replicative cellular senescence (CS) is well known and as a result, the involvement of telomerase and in particular its catalytic subunit, the telomerase reverse transcriptase (TERT) in CS has also been investigated. However, the majority of studies were conducted on cells that generally express high levels of TERT (cancer and immortalized cells) while the role of telomerase in CS in normal cells has been investigated to a much lesser extent. In particular, it was reported that active TERT is expressed in early passages of cultured human keratinocytes but rapidly diminished towards entry to CS, without telomere shortening...
March 1, 2017: Biogerontology
https://www.readbyqxmd.com/read/28212542/two-stage-genome-wide-association-study-identifies-a-novel-susceptibility-locus-associated-with-melanoma
#12
Katherine J Ransohoff, Wenting Wu, Hyunje G Cho, Harvind C Chahal, Yuan Lin, Hong-Ji Dai, Christopher I Amos, Jeffrey E Lee, Jean Y Tang, David A Hinds, Jiali Han, Qingyi Wei, Kavita Y Sarin
Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28195144/concomitant-underexpression-of-tgfbr2-and-overexpression-of-htert-are-associated-with-poor-prognosis-in-cervical-cancer
#13
Hui Yang, Hongyan Zhang, Yahua Zhong, Qiaoli Wang, Lei Yang, Hong Kang, Xiaojia Gao, Haijun Yu, Conghua Xie, Fuxiang Zhou, Yunfeng Zhou
The human telomerase reverse transcriptase (hTERT) is highly expressed in a variety of tumors. The transforming growth factor beta receptor type II (TGFBR2) is a downstream protein of transforming growth factor beta (TGF-β) which suppresses telomerase activity. However, the relevance of survival to the expression of TGFBR2, hTERT or TGFBR2/hTERT has not been previously investigated in cervical cancer tissues. Our study showed that patients with low level of TGFBR2 were associated with poor prognosis (HR = 1...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192371/somatic-mutations-in-telomerase-promoter-counterbalance-germline-loss-of-function-mutations
#14
Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A Newton, Cindy Barba, Nicolai S C van Oers, Richard C Wang, Christine Kim Garcia
Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28184371/transcriptional-regulation-of-telomerase-reverse-transcriptase-tert-by-myc
#15
REVIEW
Ekta Khattar, Vinay Tergaonkar
Telomerase elongates telomeres and is crucial for maintaining genomic stability. While stem cells and cancer cells display high telomerase activity, normal somatic cells lack telomerase activity primarily due to transcriptional repression of telomerase reverse transcriptase (TERT), the catalytic component of telomerase. Transcription factor binding, chromatin status as well as epigenetic modifications at the TERT promoter regulates TERT transcription. Myc is an important transcriptional regulator of TERT that directly controls its expression by promoter binding and associating with other transcription factors...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28154186/structural-analysis-reveals-the-deleterious-effects-of-telomerase-mutations-in-telomerase-associated-bone-marrow-failure-syndromes
#16
Hunter Hoffman, Cory Rice, Emmanuel Skordalakes
Naturally occurring mutations in the ribonucleoprotein reverse transcriptase, telomerase, are associated with the bone marrow failure syndromes dyskeratosis congenita (DKC), aplastic anemia (AA), and idiopathic pulmonary fibrosis (IPF). However, the mechanism by which these mutations impact telomerase function remains unknown. Here we present the structure of the human telomerase c-terminal extension (CTE or thumb domain) determined by the method of single-wavelength anomalous diffraction (SAD) to 2.31 A resolution...
February 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28151853/clinicopathological-characteristics-of-tert-promoter-mutation-and-telomere-length-in-hepatocellular-carcinoma
#17
Hye Won Lee, Tae In Park, Se Young Jang, Soo Young Park, Won-Jin Park, Soo-Jung Jung, Jae-Ho Lee
Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28141967/telomerase-mechanism-of-telomere-synthesis
#18
R Alex Wu, Heather E Upton, Jacob M Vogan, Kathleen Collins
Telomerase is the essential reverse transcriptase required for linear chromosome maintenance in most eukaryotes. Telomerase supplements the tandem array of simple-sequence repeats at chromosome ends to compensate for the DNA erosion inherent in genome replication. The template for telomerase reverse transcriptase is within the RNA subunit of the ribonucleoprotein complex, which in cells contains additional telomerase holoenzyme proteins that assemble the active ribonucleoprotein and promote its function at telomeres...
January 30, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28135248/systematic-analysis-of-telomere-length-and-somatic-alterations-in-31-cancer-types
#19
Floris P Barthel, Wei Wei, Ming Tang, Emmanuel Martinez-Ledesma, Xin Hu, Samirkumar B Amin, Kadir C Akdemir, Sahil Seth, Xingzhi Song, Qianghu Wang, Tara Lichtenberg, Jian Hu, Jianhua Zhang, Siyuan Zheng, Roel G W Verhaak
Cancer cells survive cellular crisis through telomere maintenance mechanisms. We report telomere lengths in 18,430 samples, including tumors and non-neoplastic samples, across 31 cancer types. Telomeres were shorter in tumors than in normal tissues and longer in sarcomas and gliomas than in other cancers. Among 6,835 cancers, 73% expressed telomerase reverse transcriptase (TERT), which was associated with TERT point mutations, rearrangements, DNA amplifications and transcript fusions and predictive of telomerase activity...
March 2017: Nature Genetics
https://www.readbyqxmd.com/read/28126377/defects-in-lymphocyte-telomere-homeostasis-contribute-to-cellular-immune-phenotype-in-patients-with-cartilage-hair-hypoplasia
#20
Geraldine Aubert, Kevin A Strauss, Peter M Lansdorp, Nicholas L Rider
BACKGROUND: Mutations in the long noncoding RNA RNase component of the mitochondrial RNA processing endoribonuclease (RMRP) give rise to the autosomal recessive condition cartilage-hair hypoplasia (CHH). The CHH disease phenotype has some overlap with dyskeratosis congenita, a well-known "telomere disorder." RMRP binds the telomerase reverse transcriptase (catalytic subunit) in some cell lines, raising the possibility that RMRP might play a role in telomere biology. OBJECTIVE: We sought to determine whether a telomere phenotype is present in immune cells from patients with CHH and explore mechanisms underlying these observations...
January 23, 2017: Journal of Allergy and Clinical Immunology
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