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Telomere reverse transcriptase

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https://www.readbyqxmd.com/read/29776440/radiological-pleuroparenchymal-fibroelastosis-associated-to-limited-cutaneous-systemic-sclerosis-a-case-report
#1
D Hassoun, S Dirou, P P Arrigoni, C Durant, M Hamidou, A Néel, C Agard
BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a very rare interstitial lung disease (ILD) characterized by progressive fibrotic lesions of the visceral pleura and the sub-pleural parenchyma, affecting predominantly the upper lobes. PPFE may occur in different contextes like bone marrow or lung transplantations, but also in the context of telomeropathy with mutations of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) or regulator of telomere elongation helicase 1 (RTEL1) genes...
May 18, 2018: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29776332/telnet-a-database-for-human-and-yeast-genes-involved-in-telomere-maintenance
#2
Delia M Braun, Inn Chung, Nick Kepper, Katharina I Deeg, Karsten Rippe
BACKGROUND: The ends of linear chromosomes, the telomeres, comprise repetitive DNA sequences in complex with proteins that protects them from being processed by the DNA repair machinery. Cancer cells need to counteract the shortening of telomere repeats during replication for their unlimited proliferation by reactivating the reverse transcriptase telomerase or by using the alternative lengthening of telomeres (ALT) pathway. The different telomere maintenance (TM) mechanisms appear to involve hundreds of proteins but their telomere repeat length related activities are only partly understood...
May 18, 2018: BMC Genetics
https://www.readbyqxmd.com/read/29775593/structure-of-telomerase-with-telomeric-dna
#3
Jiansen Jiang, Yaqiang Wang, Lukas Sušac, Henry Chan, Ritwika Basu, Z Hong Zhou, Juli Feigon
Telomerase is an RNA-protein complex (RNP) that extends telomeric DNA at the 3' ends of chromosomes using its telomerase reverse transcriptase (TERT) and integral template-containing telomerase RNA (TER). Its activity is a critical determinant of human health, affecting aging, cancer, and stem cell renewal. Lack of atomic models of telomerase, particularly one with DNA bound, has limited our mechanistic understanding of telomeric DNA repeat synthesis. We report the 4.8 Å resolution cryoelectron microscopy structure of active Tetrahymena telomerase bound to telomeric DNA...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29771920/maternal-human-telomerase-reverse-transcriptase-variants-are-associated-with-preterm-labor-and-preterm-premature-rupture-of-membranes
#4
Caroline Marrs, Kevin Chesmore, Ramkumar Menon, Scott Williams
OBJECTIVE: Premature aging and short telomere lengths of fetal tissues are associated with spontaneous preterm labor (PTL) and preterm premature rupture of membranes (pPROM). Maintenance of telomere length is performed by the enzyme telomerase. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase, and its dysfunction affects telomere shortening. This study assessed whether maternal or fetal genetic variations in the hTERT gene are associated with PTL or pPROM. METHODS: A case (PTL or pPROM) control (term birth) genetic association study was conducted in 654 non-Hispanic white mothers (438 term, 162 PTL, 54 pPROM) and 502 non-Hispanic white newborns (346 term, 116 PTB, 40 pPROM)...
2018: PloS One
https://www.readbyqxmd.com/read/29771410/g-quadruplex-antibody-attenuates-human-gastric-cancer-cell-proliferation-and-promotes-apoptosis-through-htert-telomerase-pathway
#5
Y-Q Zhang, J-H Pei, S-S Shi, J Zheng, J-M Wang, X-S Guo, G-Y Cui, X-Y Wang, H-P Zhang, W-Q Hu
OBJECTIVE: To investigate the expression of G-quadruplex antibody BG4 in human gastric cancer AGS cells and assess its functions in attenuating proliferation and promoting apoptosis in gastric cancer. MATERIALS AND METHODS: BG4 high-expression gastric cancer AGS cell line was established by pEGFP-N1-BG4 transient transfection. AGS cells transfected with pEGFP-N1 plasmids were included into the pEGFP-N1 group and those not transfected with plasmids were included into the negative control group...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29759988/transient-telomerase-inhibition-with-imetelstat-impacts-dna-damage-signals-and-cell-cycle-kinetics
#6
Connor Ah Thompson, Alice Gu, Sunny Yang, Veena Mathew, Helen B Fleisig, Judy My Wong
Telomerase is the ribonucleoprotein reverse transcriptase that catalyzes the synthesis of telomeres at the ends of linear chromosomes and contributes to proper telomere-loop (T-loop) formation. Formation of the T-loop, an obligate step before cell division can proceed, requires the generation of a 3'-overhang on the G-rich strand of telomeric DNA via telomerase or C-strand specific nucleases. Here, it is discovered that telomerase activity is critical for efficient cell cycle progression using transient chemical inhibition by the telomerase inhibitor, imetelstat...
May 14, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29749098/essential-roles-of-telomerase-reverse-transcriptase-htert-in-cancer-stemness-and-metastasis
#7
REVIEW
Ricarda Hannen, Jörg W Bartsch
Maintenance of chromosomal telomere length is a hallmark of cancer cells and a prerequisite for stemness. In 85-90% of all human cancers, telomere length maintenance is achieved by reactivation of telomerase, whereas in the remaining 10-15% cancers, alternative lengthening of telomeres (ALT) is observed. Reactivation of telomerase occurs by various mechanisms, one of which is accumulation of point mutations in the promoter region of the gene encoding the protein subunit hTERT. There are numerous studies linking either hTERT overexpression or the presence of hTERT mutations to an aggressive phenotype of several human cancers...
May 10, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29748384/balance-between-senescence-and-apoptosis-is-regulated-by-telomere-damage-induced-association-between-p16-and-caspase-3
#8
Shanmugam Panneer Selvam, Braden M Roth, Rose Nganga, Jisun Kim, Marion A Cooley, Kristi L Helke, Charles D Smith, Besim Ogretmen
Telomerase activation protects cells from telomere damage by delaying senescence and inducing cell immortalization, whereas telomerase inhibition mediates rapid senescence or apoptosis. However, the cellular mechanisms that determine telomere damage-dependent senescence versus apoptosis induction are largely unknown. Here, we demonstrate that telomerase instability mediated by silencing of sphingosine kinase 2 (SPHK2) and sphingosine 1-phosphate (S1P), which binds and stabilizes telomerase, induces telomere damage-dependent caspase-3 activation and apoptosis, but not senescence, in p16-deficient lung cancer cells or tumors...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29722072/htert-promotes-tumor-progression-by-enhancing-tspan13-expression-in-osteosarcoma-cells
#9
Rishi Kumar Jaiswal, Pramod Kumar, Manoj Kumar, Pramod Kumar Yadava
Telomerase complex maintains the length of the telomere and protects erosion of the physical ends of the eukaryotic chromosome in all actively dividing cells including cancer cells. Telomerase activation extends the lifespan of cells in culture by maintaining the length of the telomere. Compared to terminally differentiated somatic cells, telomerase activity remains high in over 90% of cancer cells. It has now become clear that the role of telomerase is much more complex than just telomere lengthening. The remaining 10% of cancers deploy ALT (alternative lengthening of telomeres) pathway to maintain telomere length...
May 2, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29717462/ddtrap-a-method-for-sensitive-and-precise-quantification-of-telomerase-activity
#10
Andrew T Ludlow, Dawne Shelton, Woodring E Wright, Jerry W Shay
Telomerase is a cellular RNA template-dependent reverse transcriptase that adds telomere repeats to the 3' ends of chromosomes. Telomerase is expressed almost universally in tumor cells (>85%) to maintain telomere length, thus providing the ability of tumor cells to avoid senescence and to have unlimited replication ability, one of the key hallmarks of cancer. ddTRAP (droplet digital Telomere Repeat Amplification Protocol) is a two-step assay with whole cell lysates that utilizes a telomerase-mediated primer extension followed by droplet digital PCR (ddPCR) detection of extended products...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29717455/simultaneous-quantification-of-multiple-alternatively-spliced-mrna-transcripts-using-droplet-digital-pcr
#11
Bing Sun, Yun-Ling Zheng
Currently there is no sensitive, precise, and reproducible method to quantitate alternative splicing of mRNA transcripts. Droplet digital™ PCR (ddPCR™) analysis allows for accurate digital counting for quantification of gene expression. Human telomerase reverse transcriptase (hTERT) is one of the essential components required for telomerase activity and for the maintenance of telomeres. Several alternatively spliced forms of hTERT mRNA in human primary and tumor cells have been reported in the literature...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29707886/telomerase-reverse-transcriptase-suppression-inhibits-cell-proliferation-and-promotes-cell-apoptosis-in-hepatocellular-cancer
#12
Yanfeng Shen, Feng Xi, Haibin Li, Yin Luo, Cheng Chen, Lei Wang
We aimed to investigate the role of telomerase reverse transcriptase (TERT) in hepatocellular cancer (HCC) cells. R software was used for differential expressed gene analysis. Western blot and quantitative real time polymerase chain reaction (qRT-PCR), respectively, were used to detect protein expression and mRNA level of TERT in tumor cell lines. Real-time quantitative telomeric repeat amplification protocol assay, MTT assay, colony formation assay, and flow cytometry (FCM) assay were used to analyze the telomerase activity, viability, proliferation, cell cycle progression and apoptosis of HCC cells...
April 29, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29705126/the-mre11a470t-mutation-and-homeologous-interactions-increase-error-prone-bir
#13
In-Joon Baek, Courtney Parke, Arthur J Lustig
In the absence of the RNA-templated reverse transcriptase, telomerase, the predominant means of terminal addition, arises from break-induced replication (BIR) at multiple homologous subtelomeric Y' loci and among internal homeologous (imperfect) (polyG1-3T) tracts. These last tracts are interspersed between subtelomeric Y' direct repeats. One major survivor class contains very short (~50 bp) terminal telomere repeats. This size is sufficient for slow growth and partial telomere functionality and cell viability...
April 26, 2018: Gene
https://www.readbyqxmd.com/read/29703210/telomerase-regulation-by-the-long-non-coding-rna-h19-in-human-acute-promyelocytic-leukemia-cells
#14
Joëlle El Hajj, Eric Nguyen, Qingyuan Liu, Claire Bouyer, Eric Adriaenssens, George Hilal, Evelyne Ségal-Bendirdjian
BACKGROUND: Since tumor growth requires reactivation of telomerase (hTERT), this enzyme is a challenging target for drug development. Therefore, it is of great interest to identify telomerase expression and activity regulators. Retinoids are well-known inducers of granulocytic maturation associated with hTERT repression in acute promyelocytic leukemia (APL) blasts. In a maturation-resistant APL cell line, we have previously identified a new pathway of retinoid-induced hTERT transcriptional repression independent of differentiation...
April 27, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29695869/cryo-em-structure-of-substrate-bound-human-telomerase-holoenzyme
#15
Thi Hoang Duong Nguyen, Jane Tam, Robert A Wu, Basil J Greber, Daniel Toso, Eva Nogales, Kathleen Collins
The enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, and ageing, but progress towards clinical manipulation of telomerase has been hampered by the lack of structural data. Here we present the cryo-electron microscopy structure of the substrate-bound human telomerase holoenzyme at subnanometre resolution, showing two flexibly RNA-tethered lobes: the catalytic core with telomerase reverse transcriptase (TERT) and conserved motifs of telomerase RNA (hTR), and an H/ACA ribonucleoprotein (RNP)...
April 25, 2018: Nature
https://www.readbyqxmd.com/read/29657298/a-novel-long-non-coding-rna-in-the-htert-promoter-region-regulates-htert-expression
#16
Sanandan Malhotra, Mallory A Freeberg, Shelby J Winans, James Taylor, Karen L Beemon
A novel antisense transcript was identified in the human telomerase reverse transcriptase ( hTERT ) promoter region, suggesting that the hTERT promoter is bidirectional. This transcript, named hTERT antisense promoter-associated ( hTAPAS ) RNA, is a 1.6 kb long non-coding RNA. hTAPAS transcription is initiated 167 nucleotides upstream of the hTERT transcription start site and is present in both the nucleus and the cytoplasm. Surprisingly, we observed that a large fraction of the hTERT polyadenylated RNA is localized in the nucleus, suggesting this might be an additional means of regulating the cellular abundance of hTERT protein...
December 29, 2017: Non-Coding RNA
https://www.readbyqxmd.com/read/29614790/microrna-regulation-of-telomerase-reverse-transcriptase-tert-micro-machines-pull-strings-of-papier-m%C3%A3-ch%C3%A3-puppets
#17
REVIEW
Ammad Ahmad Farooqi, Qaisar Mansoor, Nada Alaaeddine, Baojun Xu
Substantial fraction of high-quality information is continuously being added into the existing pool of knowledge related to the biology of telomeres. Based on the insights gleaned from decades of research, it is clear that chromosomal stability needs a highly controlled and dynamic balance of DNA gain and loss in each terminal tract of telomeric repeats. Telomeres are formed by tandem repeats of TTAGGG sequences, which are gradually lost with each round of division of the cells. Targeted inhibition of telomerase to effectively induce apoptosis in cancer cells has attracted tremendous attention and overwhelmingly increasingly list of telomerase inhibitors truthfully advocates pharmacological significance of telomerase...
April 1, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29602239/inflammatory-factor-receptor-toll-like-receptor-4-controls-telomeres-through-heterochromatin-protein-1-isoforms-in-liver-cancer-stem-cell
#18
Qidi Zheng, Jie Xu, Zhuojia Lin, Yanan Lu, Xiaoru Xin, Xiaonan Li, Yuxin Yang, Qiuyu Meng, Chen Wang, Wujun Xiong, Dongdong Lu
Toll-like receptor 4 (TLR4) which acts as a receptor for lipopolysaccharide (LPS) has been reported to be involved in carcinogenesis. However, the regulatory mechanism of it has not been elucidated. Herein, we demonstrate that TLR4 promotes the malignant growth of liver cancer stem cells. Mechanistically, TLR4 promotes the expression of histone-lysine N-methyltransferase (SUV39 h2) and increases the formation of trimethyl histone H3 lysine 9-heterochromatin protein 1-telomere repeat binding factor 2 (H3K9me3-HP1-TRF2) complex at the telomeric locus under mediation by long non coding RNA urothelial cancer-associated 1 (CUDR)...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29599138/telomerase-mediates-lymphocyte-proliferation-but-not-the-atherosclerosis-suppressive-potential-of-regulatory-t-cells
#19
Gavin Richardson, Andrew Sage, Karim Bennaceur, Nayef Al Zhrany, Jose Coelho-Lima, Emily Dookun, Lilia Draganova, Gabriele Saretzki, David T Breault, Ziad Mallat, Ioakim Spyridopoulos
OBJECTIVE: Atherosclerosis is an age-related disease characterized by systemic oxidative stress and low-grade inflammation. The role of telomerase and telomere length in atherogenesis remains contentious. Short telomeres of peripheral leukocytes are predictive for coronary artery disease. Conversely, attenuated telomerase has been demonstrated to be protective for atherosclerosis. Hence, a potential causative role of telomerase in atherogenesis is critically debated. APPROACH AND RESULTS: In this study, we used multiple mouse models to investigate the regulation of telomerase under oxidative stress as well as its impact on atherogenesis in vitro and in vivo...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29571043/transposon-control-mechanisms-in-telomere-biology
#20
REVIEW
Maria Kordyukova, Ivan Olovnikov, Alla Kalmykova
The ends of linear eukaryotic chromosomes, telomeres, are elongated by reverse transcriptase activity provided by the enzyme telomerase, or by specialized telomeric retrotransposons. Telomerase and telomeric retrotransposons represent unique examples of structurally different, but evolutionary and functionally related machineries that generate essential chromosome structures, namely telomeres. In fact, the telomere is an example of the taming of retroelements for the maintenance of essential genome function...
March 20, 2018: Current Opinion in Genetics & Development
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