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Telomere and telomerase

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https://www.readbyqxmd.com/read/28529542/frequency-and-geographic-distribution-of-tert-promoter-mutations-in-primary-hepatocellular-carcinoma
#1
REVIEW
Francesca Pezzuto, Luigi Buonaguro, Franco M Buonaguro, Maria Lina Tornesello
Primary hepatocellular carcinoma (HCC) mainly develops in subjects chronically infected with hepatitis B (HBV) and C (HCV) viruses through a multistep process characterized by the accumulation of genetic alterations in the human genome. Nucleotide changes in coding regions (i.e. TP53, CTNNB1, ARID1A and ARID2) as well as in non-coding regions (i.e. TERT promoter) are considered cancer drivers for HCC development with variable frequencies in different geographic regions depending on the etiology and environmental factors...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28521363/a-cisplatin-derivative-tetra-pt-bpy-as-an-oncotherapeutic-agent-for-targeting-alt-cancer
#2
Xiao-Hui Zheng, Xin Nie, Yiming Fang, Zepeng Zhang, Yingnan Xiao, Zongwan Mao, Haiying Liu, Jian Ren, Feng Wang, Lixin Xia, Junjiu Huang, Yong Zhao
Background: In approximately 15% of human cancers, telomere length is maintained independently of telomerase by the homologous recombination (HR)-mediated alternative lengthening of telomeres (ALT) pathway. Whether the ALT pathway can be exploited for therapeutic treatment remains unknown. The purpose of this study is to develop oncotherapeutic agent to target ALT cancers. Methods: Surface plasmon resonance assay, antibody to G-quadruplex, and fluorescence in situ hybridization (FISH) were used to discover Tetra-Pt(bpy), a cisplatin derivative that specifically targets telomeric G-quadruplex...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28520570/long-term-exposure-to-mst-312-leads-to-telomerase-reverse-transcriptase-overexpression-in-mcf-7-breast-cancer-cells
#3
Karollyne S Morais, Ana Flávia R Guimarãesb, Doralina A R Ramos, Fábio P Silva, Diêgo M de Oliveira
Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. Therefore, antitelomerase therapy is a potentially revolutionary therapeutic strategy, and the antitumor activity of telomerase inhibitors (TI) has been studied extensively recently, mainly for breast cancer. However, the effects expected from treatment with TI will appear only after many cell divisions, but the effects of this long-term approach are unknown. In this work, the consequences of 3120 h exposure of human breast cancer cells to TI MST-312 were investigated...
May 17, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28513547/epigenetic-regulation-of-telomere-maintenance-for-therapeutic-interventions-in-gliomas
#4
REVIEW
Elisabeth Naderlinger, Klaus Holzmann
High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a common human brain tumor with poor patient outcome. Astrocytoma demonstrates two known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA) and on alternative lengthening of telomeres (ALT). ALT is associated with lower tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors by direct mutation and epigenetic activation of the hTERT promoter is well established. Here, we summarize the genetic background of TMMs in non-malignant cells and in cancer, in addition to clinical and pathological features of gliomas...
May 17, 2017: Genes
https://www.readbyqxmd.com/read/28506636/multiple-dna-interactions-contribute-to-the-initiation-of-telomerase-elongation
#5
Ahu Karademir Andersson, Cecilia Gustafsson, Roopesh Krishnankutty, Marita Cohn
Telomerase maintains telomere length and chromosome integrity by adding short tandem repeats of single-stranded DNA to the 3' ends, via reverse transcription of a defined template region of its RNA subunit. To further understand the telomerase elongation mechanism, we studied the primer utilization and extension activity of the telomerase from the budding yeast Naumovozyma castellii (Saccharomyces castellii), which displays a processive nucleotide and repeat addition polymerization. For the efficient initiation of canonical elongation, telomerase required 4nt primer 3' end complementarity to the template RNA...
May 12, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28503738/targeting-human-telomeric-g-quadruplex-dna-with-antitumour-natural-alkaloid-aristololactam-%C3%AE-d-glucoside-and-its-comparison-with-daunomycin
#6
Abhi Das, Sabyasachi Chatterjee, Gopinatha Suresh Kumar
Study on anticancer agents that act via stabilization of telomeric G-quadruplex DNA has emerged as novel and exciting field for anticancer drug discovery. The interaction of carbohydrate containing anticancer alkaloid aristololactam-β-D-glucoside (ADG) with human telomeric G-quadruplex DNA sequence was characterized by different biophysical techniques. The binding parameters were compared with daunomycin (DAN), a well-known chemotherapeutic drug. The Scatchard binding isotherms revealed noncooperative binding for both with the binding affinity values of (1...
May 15, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28500256/tzap-ing-telomeres-down-to-size
#7
Laura Garcia-Exposito, Roderick J O'Sullivan
The phenomenon of gradual telomere shortening has become a paradigm for how we understand the biology of aging and cancer. Cell proliferation is accompanied by cumulative telomere loss, and the aged cell either senesces, dies or transforms toward cancer. This transformation requires the activation of telomere elongation mechanisms in order to restore telomere length such that cell death or senescence programs are not induced. Most of the time, this occurs through telomerase reactivation. In other rare cases, the Alternative lengthening of telomeres (ALT) pathway hijacks DNA recombination-associated mechanisms to hyperextend telomeres, often to more than 50 kb...
May 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28495680/dna-binding-determinants-and-cellular-thresholds-for-human-telomerase-repeat-addition-processivity
#8
Robert Alexander Wu, Jane Tam, Kathleen Collins
The reverse transcriptase telomerase adds telomeric repeats to chromosome ends. Purified human telomerase catalyzes processive repeat synthesis, which could restore the full ~100 nucleotides of (T2AG3)n lost from replicated chromosome ends as a single elongation event. Processivity inhibition is proposed to be a basis of human disease, but the impacts of different levels of processivity on telomere maintenance have not been examined. Here, we delineate side chains in the telomerase active-site cavity important for repeat addition processivity, determine how they contribute to duplex and single-stranded DNA handling, and test the cellular consequences of partial or complete loss of repeat addition processivity for telomere maintenance...
May 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28493234/exploration-of-involved-key-genes-and-signaling-diversity-in-brain-tumors
#9
REVIEW
Mojdeh Mahdian Nasser, Parvin Mehdipour
Brain tumors are becoming a major cause of death. The classification of brain tumors has gone through restructuring with regard to some criteria such as the presence or absence of a specific genetic alteration in the 2016 central nervous system World Health Organization update. Two categories of genes with a leading role in tumorigenesis and cancer induction include tumor suppressor genes and oncogenes; tumor suppressor genes are inactivated through a variety of mechanisms that result in their loss of function...
May 10, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28487971/azidothymidine-inhibits-cell-growth-and-telomerase-activity-and-induces-dna-damage-in-human-esophageal-cancer
#10
Haoli Wang, Jianwen Zhou, Qiong He, Yu Dong, Yanhui Liu
Esophageal cancer is one of the most common type of malignancies. Telomerase activity, which is absent or weakly detected in the majority of human somatic cells, is elevated in esophageal cancer. Although azidothymidine (AZT), a reverse transcriptase inhibitor, has been utilized as a treatment for tumors, its role in treating esophageal cancer has not been confirmed. The aim of the present study was to determine the effect of AZT on telomerase activity and the proliferation of the human esophageal cancer cell line TE‑11...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28483909/progerin-induced-replication-stress-facilitates-premature-senescence-in-hutchinson-gilford-progeria-syndrome
#11
Keith Wheaton, Denise Campuzano, Weili Ma, Michal Sheinis, Brandon Ho, Grant W Brown, Samuel Benchimol
Hutchinson-Gilford progeria syndrome (HGPS) is caused by a mutation in LMNA that produces an aberrant lamin A protein, progerin. The accumulation of progerin in HGPS cells leads to an aberrant nuclear morphology, genetic instability and p53-dependent premature senescence. How p53 is activated in response to progerin production is unknown. Here, we show that young, cycling HGPS fibroblasts, exhibit chronic DNA damage primarily in S phase as well as delayed replication fork progression. We demonstrate that progerin binds to PCNA altering its distribution away from replicating DNA in HGPS cells leading to γH2AX formation, ATR activation and RPA Ser33 phosphorylation...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483762/clonal-hematopoiesis-with-and-without-candidate-driver-mutations-is-common-in-the-elderly
#12
Florian Zink, Simon N Stacey, Gudmundur L Norddahl, Michael L Frigge, Olafur T Magnusson, Ingileif Jonsdottir, Thorgeir E Thorgeirsson, Asgeir Sigurdsson, Sigurjon A Gudjonsson, Julius Gudmundsson, Jon G Jonasson, Laufey Tryggvadottir, Thorvaldur Jonsson, Agnar Helgason, Arnaldur Gylfason, Patrick Sulem, Thorunn Rafnar, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Gisli Masson, Augustine Kong, Kari Stefansson
Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells are derived from a single dominant hematopoietic stem cell lineage. Somatic mutations in candidate driver (CD) genes are thought to be responsible for at least some cases of CH. Using whole genome sequencing of 11,262 Icelanders, we found 1,403 cases of CH by using barcodes of mosaic somatic mutations in peripheral blood, irrespective of whether or not they have a mutation in a CD gene. We find that CH is very common in the elderly, trending towards inevitability...
May 8, 2017: Blood
https://www.readbyqxmd.com/read/28482242/does-telomerase-activity-have-an-effect-on-infertility-in-patients-with-endometriosis
#13
Nigar Sofiyeva, Seda Ekizoglu, Altay Gezer, Handan Yilmaz, Tugba Kolomuc Gayretli, Nur Buyru, Engin Oral
OBJECTIVE: This study aimed to investigate the role of telomerase activity in the development of endometriosis-related infertility by evaluation of the serum telomerase in eutopic and ectopic endometrial tissue. STUDY DESIGN: Eutopic endometrium, cystic wall/ovarian cortex, and venous blood were assessed in forty-seven patients. The following groups of patients were identified: females with endometriosis requiring surgical intervention and healthy control females...
April 18, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28479693/telomeres-in-health-and-disease
#14
REVIEW
Shailja Chatterjee
Telomeres are repetitive ribonucleoprotein complexes present at ends of chromosomes. To synthesize this manuscript, a thorough literature search was done using PubMed, MEDLINE and Cochrane review for English-language literature and data available from the period of 2005-2016 were analyzed for manuscript writing. Telomeres help in maintaining the cellular health, inbuilt cellular mechanisms, metabolism and normal cell cycle. Telomerase is a specialized enzyme that possesses catalytic subunits - reverse transcriptase, Terc and dyskerin...
January 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/28479277/selectivity-of-major-isoquinoline-alkaloids-from-chelidomium-majus-towards-telomeric-g-quadruplex-a-study-using-a-modified-transition-fret-t-fret-assay
#15
Sakineh Kazemi Noureini, Hosein Esmaeili, Farzane Abachi, Soraia Khiali, Barira Islam, Martyna Kuta, Ali A Saboury, Marcin Hoffmann, Jiri Sponer, Gary Parkinson, Shozeb Haider
BACKGROUND: Natural bioproducts are invaluable resources in drug discovery. Isoquinoline alkaloids of Chelidonium majus constitute a structurally diverse family of natural products that are of great interest, one of them being their selectivity for human telomeric G-quadruplex structure and telomerase inhibition. METHODS: The study focuses on the mechanism of telomerase inhibition by stabilization of telomeric G-quadruplex structures by berberine, chelerythrine, chelidonine, sanguinarine and papaverine...
May 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28477298/telomere-length-is-short-in-pcos-and-oral-contraceptive-does-not-affect-the-telomerase-activity-in-granulosa-cells-of-patients-with-pcos
#16
Ying Li, Bingbing Deng, Nengyong Ouyang, Ping Yuan, Lingyan Zheng, Wenjun Wang
PURPOSE: Our study aimed to investigate the association of telomerase activity (TA) and telomere length (TL) in granulosa cells (GCs) with IVF outcomes of polycystic ovary syndrome (PCOS) patients, and the effects of oral contraceptive pill (OCP) pretreatment on these two parameters. METHODS: One hundred sixty-three infertile women were enrolled and divided into a PCOS group (n = 65) and a non-PCOS group (n = 98). The PCOS group was further divided into an OCP pretreatment group (n = 35) and a non-OCP pretreatment group (n = 30), a TA <0...
May 6, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28476011/arylsulfanyl-groups-suitable-side-chains-for-5-substituted-1-10-phenanthroline-and-nickel-complexes-as-g4-ligands-and-telomerase-inhibitors
#17
Wanbo Liu, Siwen Wang, Irina A Dotsenko, Vyacheslav V Samoshin, Liang Xue
Guanine-rich DNA sequences can undergo self-assembly into unique G-quadruplex structures that interfere with the binding of proteins to the same DNA region. The formation of DNA G-quadruplexes requires monovalent cations (Na(+) and K(+)) or small molecules known as G-quadruplex (G4) ligands. Phenanthroline is a type of G4 ligand scaffold known for its coordination with metal ions to form complexes with a large aromatic surface area, which aptly stack with G-quartets. In this report, we have investigated the side chain effect on G-quadruplex recognition by evaluating a series of 5-substituted phenanthroline-based metal complexes (Phen-Ni) binding to telomeric G-quadruplex DNA...
April 27, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28471262/mtv-sings-jubilation-for-telomere-biology-in-drosophila
#18
Lin Cheng, Ming Cui, Yikang S Rong
Telomere protects the ends of linear chromosomes. Telomere dysfunction fuels genome instability that can lead to diseases such as cancer. For over 30 years, Drosophila has fascinated the field as the only major model organism that does not rely on the conserved telomerase enzyme for end protection. Instead of short DNA repeats at chromosome ends, Drosophila has domesticated retrotransposons. In addition, telomere protection can be entirely sequence-independent under normal laboratory conditions, again dissimilar to what has been established for telomerase-maintained systems...
May 4, 2017: Fly
https://www.readbyqxmd.com/read/28469639/telomerase-and-mtor-in-the-brain-the-mitochondria-connection
#19
REVIEW
Satomi Miwa, Gabriele Saretzki
Telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component. Additionally, the protein part TERT (Telomerase Reverse Transcriptase) has various non-canonical functions. For example, it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress, DNA damage and apoptosis. Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28468887/stabilization-of-telomere-g-quadruplexes-interferes-with-human-herpesvirus-6a-chromosomal-integration
#20
Shella Gilbert-Girard, Annie Gravel, Sara Artusi, Sara N Richter, Nina Wallaschek, Benedikt B Kaufer, Louis Flamand
Human herpesvirus 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6 integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevent telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex specific antibodies and surface plasmon resonance...
May 3, 2017: Journal of Virology
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