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Telomere reverse transcriptase

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https://www.readbyqxmd.com/read/28212542/two-stage-genome-wide-association-study-identifies-a-novel-susceptibility-locus-associated-with-melanoma
#1
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
#2
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
#3
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...
February 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28184371/transcriptional-regulation-of-telomerase-reverse-transcriptase-tert-by-myc
#4
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
#5
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
#6
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
#7
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
#8
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...
January 30, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28126377/defects-in-lymphocyte-telomere-homeostasis-contribute-to-cellular-immune-phenotype-in-cartilage-hair-hypoplasia
#9
Geraldine Aubert, Kevin A Strauss, Peter M Lansdorp, Nicholas L Rider
BACKGROUND: Mutations in the lncRNA 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 protein TERT in some cell lines, raising the possibility that RMRP may play a role in telomere biology. OBJECTIVE: We sought to determine if a telomere phenotype is present in immune cells from individuals with CHH and explore mechanisms underlying these observations...
January 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28123854/telomerase-reverse-transcriptase-tert-promoter-mutations-in-korean-melanoma-patients
#10
Mi Ryung Roh, Kyu-Hyun Park, Kee Yang Chung, Sang Joon Shin, Sun Young Rha, Hensin Tsao
Telomerase reverse transcriptase (TERT) is the reverse transcriptase component of the telomeric complex, which synthesizes terminal DNA to protect chromosomal ends and to maintain genomic integrity. In melanoma, mutation in TERT promoter region is a common event and theses promoter variants have been shown to be associated with increased gene expression, decreased telomere length and poorer outcome. In this study, we determined the frequency of TERT promoter mutation in 88 Korean primary melanoma patients and aimed to see the association of TERT promoter mutation status to other major molecular features, such as BRAF, NRAS, KIT mutations and correlate with clinicopathological features...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28115201/life-and-death-of-yeast-telomerase-rna
#11
REVIEW
Yulia Vasianovich, Raymund J Wellinger
Telomerase reverse transcriptase elongates telomeres to overcome their natural attrition and allow unlimited cellular proliferation, a characteristic shared by stem cells as well as the majority of malignant cancerous cells. The telomerase holoenzyme comprises a core RNA molecule, a catalytic protein subunit and other accessory proteins. Malfunction of certain telomerase components can cause serious genetic disorders including dyskeratosis congenita and aplastic anemia. A hierarchy of tightly regulated steps constitute the process of telomerase biogenesis, which if interrupted or misregulated, can impede production of a functional enzyme and severely affect telomere maintenance...
January 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#12
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
#13
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/28050263/peculiarities-of-yeasts-and-human-telomerase-rnas-processing
#14
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
#15
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...
February 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28038469/polyunsaturated-fatty-acids-ameliorate-aging-via-redox-telomere-antioncogene-axis
#16
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...
January 31, 2017: 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
#17
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/28006764/telomere-dysfunction-in-nonalcoholic-fatty-liver-disease-and-cryptogenic-cirrhosis
#18
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...
2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28002788/tianshengyuan-1-tsy-1-regulates-cellular-telomerase-activity-by-methylation-of-tert-promoter
#19
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...
January 31, 2017: Oncotarget
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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