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Telomere and telomerase

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https://www.readbyqxmd.com/read/28815538/long-noncoding-rnas-in-the-yeast-s-%C3%A2-cerevisiae
#1
Rachel O Niederer, Evan P Hass, David C Zappulla
Long noncoding RNAs have recently been discovered to comprise a sizeable fraction of the RNA World. The scope of their functions, physical organization, and disease relevance remain in the early stages of characterization. Although many thousands of lncRNA transcripts recently have been found to emanate from the expansive DNA between protein-coding genes in animals, there are also hundreds that have been found in simple eukaryotes. Furthermore, lncRNAs have been found in the bacterial and archaeal branches of the tree of life, suggesting they are ubiquitous...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815183/pinx1-is-a-potential-prognostic-factor-for-non-small-cell-lung-cancer-and-inhibits-cell-proliferation-and-migration
#2
Shengguang Wang, Hua Zhang, Jianquan Zhu, Chenguang Li, Jinfang Zhu, Bowen Shi, Bin Zhang, Changli Wang
PinX1 has been identified as a suppressor of telomerase enzymatic activity. However, the tumour-suppressive roles of PinX1 in different types of human cancers are unclear. PinX1 expression status and its correlation with clinicopathological features in non-small-cell lung cancer (NSCLC) have not been investigated. Accordingly, in this study, we aimed to evaluate the roles of PinX1 in NSCLC. PinX1 expression status was examined by immunohistochemistry using tissue microarray from a total of 158 patients. Correlations among PinX1 expression, clinicopathological variables, and patient survival were analysed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#3
Flávia S Donaires, Natália F Scatena, Raquel M Alves-Paiva, Joshua D Podlevsky, Dhenugen Logeswaran, Barbara A Santana, Andreza C Teixeira, Julian J-L Chen, Rodrigo T Calado, Ana L C Martinelli
Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28807855/spatial-organization-and-molecular-interactions-of-the-schizosaccharomyces-pombe-ccq1-tpz1-poz1-shelterin-complex
#4
Harry Scott, Jin-Kwang Kim, Clinton Yu, Lan Huang, Feng Qiao, Derek J Taylor
The shelterin complex is a macromolecular assembly of proteins that binds to and protects telomeric DNA, which composes the ends of all linear chromosomes. Shelterin proteins prevent chromosome ends from fusing together and from eliciting erroneous induction of DNA damage response pathways. Additionally, shelterin proteins play key roles in regulating the recruitment and activation of telomerase, an enzyme that extends telomeric DNA. In fission yeast, Schizosaccharomyces pombe, interactions between the shelterin proteins Ccq1, Tpz1, and Poz1, are important for regulating telomerase-mediated telomere synthesis, and thus, telomere length homeostasis...
August 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28792435/regulation-of-telomere-homeostasis-during-epstein-barr-virus-infection-and-immortalization
#5
REVIEW
Siamak A Kamranvar, Maria G Masucci
The acquisition of unlimited proliferative potential is dependent on the activation of mechanisms for telomere maintenance, which counteracts telomere shortening and the consequent triggering of the DNA damage response, cell cycle arrest, and apoptosis. The capacity of Epstein Barr virus (EBV) to infect B-lymphocytes in vitro and transform the infected cells into autonomously proliferating immortal cell lines underlies the association of this human gamma-herpesvirus with a broad variety of lymphoid and epithelial cell malignancies...
August 9, 2017: Viruses
https://www.readbyqxmd.com/read/28781951/ifitm1-suppresses-expression-of-human-endogenous-retroviruses-in-human-embryonic-stem-cells
#6
Yudong Fu, Zhongcheng Zhou, Hua Wang, Peng Gong, Renpeng Guo, Jinmiao Wang, Xinyi Lu, Feng Qi, Lin Liu
Interferon-induced transmembrane protein 1 (IFITM1), a member of the IFITM protein family, is a component of a multimeric complex involved in the transduction of antiproliferation and cell adhesion signals. IFITM1 is thought to play a role in antiproliferation and immune surveillance, and has been shown to restrict infection by numerous viruses. It is highly expressed in human embryonic stem cells (hESCs) but its role in hESCs remains to be elucidated. In this study, knockout of IFITM1 mediated by CRISPR/Cas9 in hESCs did not affect self-renewal, pluripotency, telomerase activity or telomeres...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28780613/mec1-atr-is-needed-for-extensive-telomere-elongation-in-response-to-ethanol-in-yeast
#7
Yaniv Harari, Martin Kupiec
Telomere length homeostasis is essential for cell survival. In humans, telomeres shorten as a function of age. Short telomeres are known determinants of cell senescence and longevity. The yeast Saccharomyces cerevisiae expresses telomerase and maintains a strict telomere length homeostasis during vegetative growth. We have previously reported that different environmental signals promote changes in telomere length in S. cerevisiae. In particular, exposure to ethanol induces an extensive telomere elongation response due to a reduction in RAP1 mRNA and protein levels...
August 5, 2017: Current Genetics
https://www.readbyqxmd.com/read/28776613/an-ultra-sensitive-colorimetric-assay-for-reliable-visual-detection-of-telomerase-activity
#8
Yaocai Wang, Luzhu Yang, Yanjun Wang, Wei Liu, Baoxin Li, Yan Jin
The visual detection of a disease biomarker is a promising strategy due to its simplicity and low cost, but the complexity of biological samples limits its application. Herein, a reliable and ultrasensitive colorimetric assay was proposed for detecting telomerase activity in crude cancer cell extracts. A telomerase substrate (TS) primer was immobilized onto magnetic beads (MBs) to form a MB/TS complex. In the presence of telomerase and deoxyribonucleotide triphosphates (dNTPs), the TS primer was elongated by adding multiple telomeric repeats (TTAGGG)n to the 3' end of the TS...
August 4, 2017: Analyst
https://www.readbyqxmd.com/read/28765565/telomerase-reverse-transcriptase-promotes-chemoresistance-by-suppressing-cisplatin-dependent-apoptosis-in-osteosarcoma-cells
#9
Zhengpei Zhang, Ling Yu, Guo Dai, Kezhou Xia, Gaiwei Liu, Qi Song, Chunjie Tao, Tian Gao, Weichun Guo
Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing decreased apoptosis and increased resistance against DNA damage. Elucidation of the molecular mechanisms underlying this effect is critical to improve treatment outcomes. Previously, our group showed higher telomerase reverse transcriptase(TERT) expression in cisplatin resistant osteosarcoma cells...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765174/role-of-telomeric-repeat-containing-rna-in-telomeric-chromatin-remodeling-during-the-early-expansion-of-human-embryonic-stem-cells
#10
Sicong Zeng, Lvjun Liu, Yi Sun, Guangxiu Lu, Ge Lin
This study aimed to explore the role of telomeric repeat-containing RNA (TERRA) in telomeric chromatin remodeling during the early expansion of human embryonic stem cells (hESCs). During the derivation of hESCs, histone demethylation in the telomeric region facilitates telomerase-mediated telomere elongation. An adequate telomere repeat is essential for hESCs to acquire and/or maintain the unlimited symmetric division, which suggests that there is a link between pluripotency and telomere maintenance. The present study found that the gradual decrease in TERRA levels and related TERRA foci were correlated with telomeric length elongation in the early expansion of hESCs...
August 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28765009/involvement-of-trnas-in-replication-of-human-mitochondrial-dna-and-modifying-effects-of-telomerase
#11
Meenakshisundaram Balasubramaniam, Robert J Shmookler Reis, D Phil, Srinivas Ayyadevara, Xianwei Wang, Akshatha Ganne, Magomed Khaidakov
Overexpression of telomerase has been shown to significantly increase the lifespan of mice. When mechanistically attributed to repair of critically short telomeres, the lifespan extending action of telomerase cannot be reconciled with the observation that telomerase-null mice do not exhibit shortening of lifespan for at least two generations. We hypothesized that telomerase may interfere with replication of mitochondrial DNA (mtDNA) in a way that reduces formation of deletions - the primary cause of age-dependent cell attrition in non-renewable cells such as myocytes and neurons...
July 29, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28760773/alternative-lengthening-of-telomeres-mediated-by-mitotic-dna-synthesis-engages-break-induced-replication-processes
#12
Jaewon Min, Woodring E Wright, Jerry W Shay
Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that occurs in a subset of cancers. By analyzing telomerase positive cells and their hTERC knockout derived ALT human cell lines, we show that ALT cells harbor more fragile telomeres representing telomere replication problems. ALT-associated replication defects trigger mitotic DNA synthesis (MiDAS) at telomeres in a RAD52-dependent, but RAD51-independent, manner. Telomeric MiDAS is a conservative DNA synthesis process, potentially mediated by break-induced replication, similar to type II ALT survivors in S...
July 31, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28757166/p53-mediates-failure-of-human-definitive-hematopoiesis-in-dyskeratosis-congenita
#13
Wilson Chun Fok, Evandro Luis de Oliveira Niero, Carissa Dege, Kirsten Ann Brenner, Christopher Michael Sturgeon, Luis Francisco Zirnberger Batista
Dyskeratosis congenita (DC) is a bone marrow failure syndrome associated with telomere dysfunction. The progression and molecular determinants of hematopoietic failure in DC remain poorly understood. Here, we use the directed differentiation of human embryonic stem cells harboring clinically relevant mutations in telomerase to understand the consequences of DC-associated mutations on the primitive and definitive hematopoietic programs. Interestingly, telomere shortening does not broadly impair hematopoiesis, as primitive hematopoiesis is not impaired in DC cells...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28755323/detection-of-the-alternative-lengthening-of-telomeres-pathway-in-malignant-gliomas-for-improved-molecular-diagnosis
#14
Anne Fogli, Marie-Véronique Demattei, Laetitia Corset, Catherine Vaurs-Barrière, Emmanuel Chautard, Julian Biau, Jean-Louis Kémény, Catherine Godfraind, Bruno Pereira, Toufik Khalil, Nathalie Grandin, Philippe Arnaud, Michel Charbonneau, Pierre Verrelle
Human malignant gliomas exhibit acquisition of either one of two telomere maintenance mechanisms, resulting from either reactivation of telomerase expression or activation of an alternative lengthening of telomeres (ALT) mechanism. In the present study, we analyzed 63 human malignant gliomas for the presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles) and measured telomerase expression, telomeric DNA content (Telo/Alu method), and telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular markers routinely used in clinical practice...
July 28, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28754961/the-maintenance-of-telomere-length-in-cd28-t-cells-during-t-lymphocyte-stimulation
#15
Ejun Elijah Huang, Enzo Tedone, Ryan O'Hara, Crystal Cornelius, Tsung-Po Lai, Andrew Ludlow, Woodring E Wright, Jerry W Shay
Telomerase activity is not readily detected in resting human T lymphocytes, however upon antigen presentation, telomerase is transiently upregulated. Presently, it is not known if telomerase activation is necessary for the proliferation of T cells or for the maintenance of telomere lengths. In this study, we found that telomerase activation is not required for the short- term proliferation of T cells and that telomeres progressively shorten in a heterogeneous population of T cells, even if telomerase is detected...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753967/drosophila-retrotransposons-making-up-telomeres
#16
REVIEW
Elena Casacuberta
Drosophila and extant species are the best-studied telomerase exception. In this organism, telomere elongation is coupled with targeted retrotransposition of Healing Transposon (HeT-A) and Telomere Associated Retrotransposon (TART) with sporadic additions of Telomere Associated and HeT-A Related (TAHRE), all three specialized non-Long Terminal Repeat (non-LTR) retrotransposons. These three very special retroelements transpose in head to tail arrays, always in the same orientation at the end of the chromosomes but never in interior locations...
July 19, 2017: Viruses
https://www.readbyqxmd.com/read/28753579/inhibitors-of-telomerase-and-poly-adp-ribose-polymerases-synergize-to-limit-the-lifespan-of-pancreatic-cancer-cells
#17
Katrina M Burchett, Asserewou Etekpo, Surinder K Batra, Ying Yan, Michel M Ouellette
Imetelstat (GRN163L) is a potent and selective inhibitor of telomerase. We have previously reported that GRN163L could shorten telomeres and limit the lifespan of CD18/HPAF and CAPAN1 pancreatic cancer cells. Here, we examined the effects of GRN163L on two other pancreatic cancer cell lines: AsPC1 and L3.6pl. In both lines, chronic exposure to GRN163L led to an initial shortening of telomeres followed by a stabilization of extremely short telomeres. In AsPC1 cells, telomere attrition eventually led to the induction of crisis and the loss of the treated population...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28752941/the-au-9-methylcaffein-8-ylidene-2-dna-tel23-system-solution-computational-and-biological-studies
#18
Francesco Papi, Carla Bazzicalupi, Marta Ferraroni, Lara Massai, Benoit Bertrand, Paola Gratteri, Donato Colangelo, Luigi Messori
The interactions occurring in solution between the dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)2]BF4, AuNHC hereafter, and a human telomeric DNA sequence (i.e. Tel23) are investigated here through different physico-chemical methods. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC; the respective binding stoichiometries and constants were determined. In turn, computational studies provide a good link between previous crystallographic results of the same system and the present solution data offering an exhaustive description of the inherent non-covalent metallodrug/DNA interactions...
July 28, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28741793/telomerase-enzyme-deficiency-promotes-metabolic-dysfunction-in-murine-hepatocytes-upon-dietary-stress
#19
Raquel M Alves-Paiva, Sachiko Kajigaya, Xingmin Feng, Jichun Chen, Marie Desierto, Susan Wong, Danielle M Townsley, Flávia S Donaires, Adeline Bertola, Bin Gao, Neal S Young, Rodrigo T Calado
Short telomeres and genetic telomerase defects are risk factors for some human liver diseases, ranging from non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) to cirrhosis. In murine models, telomere dysfunction has been shown to metabolically compromise hematopoietic cells, liver, and heart via the activation of the p53-PGC axis METHODS: Tert- and Terc-deficient mice were challenged with liquid high fat diet (HFD). Liver metabolic contents were analyzed by CE-TOFMS and liver fat content was confirmed by confocal and electronic microscopy RESULTS: Tert-deficient but not Terc-deficient mice develop hepatocyte injury and frank steatosis when challenged with liquid HFD...
July 25, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28740573/telomere-length-regulation-through-epidermal-growth-factor-receptor-signaling-in-cancer
#20
REVIEW
Titto Augustine, Radhashree Maitra, Sanjay Goel
Length of the telomere (TL), a structure at the tip of chromosome that protects and ensures stability, is determined by multi-protein complexes such as telosome/shelterin and telomerase. Earlier studies from our laboratory show that longer TL has potential to be positive predictive biomarker of clinical outcome to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy in patients with KRAS WT metastatic colorectal cancer. Although there is extensive literature suggesting the role of shelterin and telomerase, not much literature exists that describes the role of EGFR and KRAS pathway in regulating TL...
May 2017: Genes & Cancer
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