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Telomere and telomerase

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https://www.readbyqxmd.com/read/28427283/break-induced-replication-in-eukaryotes-mechanisms-functions-and-consequences
#1
Cynthia J Sakofsky, Anna Malkova
Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA...
April 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28425985/the-cellular-senescence-of-leukemia-initiating-cells-from-acute-lymphoblastic-leukemia-is-postponed-by-%C3%AE-arrestin1-binding-with-p300-sp1-to-regulate-htert-transcription
#2
Shan Liu, Haiyan Liu, Ru Qin, Yi Shu, Zhidai Liu, Penghui Zhang, Caiwen Duan, Dengli Hong, Jie Yu, Lin Zou
Although we previously reported that the self-renewal of leukemia-initiating cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by β-Arrestin1, a multiple-function protein, the cellular senescence is critical for LICs fate and leukemia progress, and worthy for further investigation. Here we found that depletion of β-Arrestin1 extended the population doubling time and the percentage of senile cells, the signatures of cellular senescence, of B-ALL LICs. Moreover, lack of β-Arrestin1 enhanced the expression of proteins (CBX, HIRA) and genes (P53, P16) related to senescence in leukemic Reh cells and B-ALL-LICs-derived leukemic mice...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#3
Yue Yu, Shashank P Katiyar, Durai Sundar, Zeenia Kaul, Eijiro Miyako, Zhenya Zhang, Sunil C Kaul, Roger R Reddel, Renu Wadhwa
Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers)...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28418989/impact-of-antiretroviral-treatment-containing-tenofovir-difumarate-on-the-telomere-length-of-aviremic-hiv-infected-patients
#4
Rocio Montejano, Natalia Stella-Ascariz, Susana Monge, José I Bernardino, Ignacio Pérez-Valero, MaLuisa Montes, Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, Juan González-García, Francisco Arnalich, Jesús Mingorance, Laura Pintado Berniches, Rosario Perona, José R Arribas
OBJECTIVE: To evaluate the in vivo relevance of the inhibitory effect of tenofovir upon telomerase activity observed in vitro. DESIGN: Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) Methods: Telomere length in whole blood was measured by quantitative real time PCR. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders RESULTS:: 200 patients included, 72% male, median age 49 (IQR 45-54...
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28412741/opposite-effects-of-gcn5-and-pcaf-knockdowns-on-the-alternative-mechanism-of-telomere-maintenance
#5
Maya Jeitany, Dalal Bakhos-Douaihy, David C Silvestre, Jose R Pineda, Nicolas Ugolin, Angela Moussa, Laurent R Gauthier, Didier Busso, Marie-Pierre Junier, Hervé Chneiweiss, Sylvie Chevillard, Chantal Desmaze, François D Boussin
Cancer cells can use a telomerase-independent mechanism, known as alternative lengthening of telomeres (ALT), to elongate their telomeres. General control non-derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF) are two homologous acetyltransferases that are mutually exclusive subunits in SAGA-like complexes. Here, we reveal that down regulation of GCN5 and PCAF had differential effects on some phenotypic characteristics of ALT cells. Our results suggest that GCN5 is present at telomeres and opposes telomere recombination, in contrast to PCAF that may indirectly favour them in ALT cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411413/sexual-intimacy-in-couples-is-associated-with-longer-telomere-length
#6
Tomás Cabeza de Baca, Elissa S Epel, Theodore F Robles, Michael Coccia, Amanda Gilbert, Eli Puterman, Aric A Prather
High-quality relationships have been shown to be beneficial for physical and mental health. This study examined overall relationship satisfaction and perceived stress as well as daily reports of partner support, partner conflict, and physical intimacy obtained over the course of one week in a sample of 129 high and low stress mothers. Telomere length was examined in whole blood, as well as the two cell subpopulations: peripheral blood mononuclear cells (PBMCs) and granulocytes. Telomerase activity was measured in PBMCs...
March 25, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28410238/physical-activity-and-telomere-length-impact-of-aging-and-potential-mechanisms-of-action
#7
REVIEW
Nicole C Arsenis, Tongjian You, Elisa F Ogawa, Grant M Tinsley, Li Zuo
Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398700/differential-requirements-for-dna-repair-proteins-in-immortalized-cell-lines-using-alternative-lengthening-of-telomere-mechanisms
#8
Alaina R Martinez, Zeenia Kaul, Jeffrey D Parvin, Joanna Groden
Cancer cells require telomere maintenance to enable uncontrolled growth. Most often telomerase is activated, although a subset of human cancers are telomerase-negative and depend on recombination-based mechanisms known as ALT (Alternative Lengthening of Telomeres). ALT depends on proteins that are essential for homologous recombination, including BLM and the MRN complex, to extend telomeres. This study surveyed the requirement for requisite homologous recombination proteins, yet to be studied in human ALT cell lines, by protein depletion using RNA interference...
April 11, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28398500/chiral-metallohelices-enantioselectively-target-hybrid-human-telomeric-g-quadruplex-dna
#9
Andong Zhao, Suzanne E Howson, Chuanqi Zhao, Jinsong Ren, Peter Scott, Chunyu Wang, Xiaogang Qu
The design and synthesis of metal complexes that can specifically target DNA secondary structure has attracted considerable attention. Chiral metallosupramolecular complexes (e.g. helicates) in particular display unique DNA-binding behavior, however until recently few examples which are both water-compatible and enantiomerically pure have been reported. Herein we report that one metallohelix enantiomer , available from a diastereoselective synthesis with no need for resolution, can enantioselectively stabilize human telomeric hybrid G-quadruplex and strongly inhibit telomerase activity with IC 50 of 600 nM...
April 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28393832/structural-insights-into-pot1-tpp1-interaction-and-pot1-c-terminal-mutations-in-human-cancer
#10
Cong Chen, Peili Gu, Jian Wu, Xianyun Chen, Shuangshuang Niu, Hong Sun, Lijie Wu, Na Li, Junhui Peng, Shaohua Shi, Cuiying Fan, Min Huang, Catherine C L Wong, Qingguo Gong, Chandan Kumar-Sinha, Rongguang Zhang, Lajos Pusztai, Rekha Rai, Sandy Chang, Ming Lei
Mammalian shelterin proteins POT1 and TPP1 form a stable heterodimer that protects chromosome ends and regulates telomerase-mediated telomere extension. However, how POT1 interacts with TPP1 remains unknown. Here we present the crystal structure of the C-terminal portion of human POT1 (POT1C) complexed with the POT1-binding motif of TPP1. The structure shows that POT1C contains two domains, a third OB fold and a Holliday junction resolvase-like domain. Both domains are essential for binding to TPP1. Notably, unlike the heart-shaped structure of ciliated protozoan Oxytricha nova TEBPα-β complex, POT1-TPP1 adopts an elongated V-shaped conformation...
April 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28389767/a-new-pot1-germline-mutation-expanding-the-spectrum-of-pot1-associated-cancers
#11
Tremika Le-Shan Wilson, Namita Hattangady, Antonio Marcondes Lerario, Carmen Williams, Erika Koeppe, Shane Quinonez, Jenae Osborne, Kelly B Cha, Tobias Else
Melanomas are associated with several hereditary conditions. We present a large family with several family members affected with primary melanomas and dysplastic nevi as well as thyroid cancer and other malignant tumors. Clinical work-up did not reveal a mutation in any of the genes usually considered with evaluation for predisposition to melanoma (BRCA1/2, CDKN2A, CDK4, PTEN, TP53). Whole exome sequencing of five affected family members showed a new variant in POT1. POT1 is associated with the telomere shelterin complex that regulates telomere protection and telomerase access...
April 7, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28376558/pfap2tel-harbouring-a-non-canonical-dna-binding-ap2-domain-binds-to-plasmodium-falciparum-telomeres
#12
Miguel Sierra-Miranda, Shruthi S Vembar, Dulce María Delgadillo, P A Ávila-López, Miguel Vargas, Rosaura Hernandez-Rivas
The telomeres of the malaria parasite Plasmodium falciparum are essential not only for chromosome end maintenance during blood stage development in humans but also to generate genetic diversity by facilitating homologous recombination of subtelomeric, multigene virulence families such as var and rifin. However, other than the telomerase PfTERT, proteins that act at P. falciparum telomeres are poorly characterized. To isolate components that bind to telomeres, we performed oligonucleotide pulldowns and electromobility shift assays with a telomeric DNA probe and identified a non-canonical member of the ApiAP2 family of transcription factors, PfAP2Tel (encoded by PF3D7_0622900), as a component of the P...
April 4, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28375735/single-molecule-studies-of-telomeres-and-telomerase
#13
Joseph W Parks, Michael D Stone
Telomeres are specialized chromatin structures that protect chromosome ends from dangerous processing events. In most tissues, telomeres shorten with each round of cell division, placing a finite limit on cell growth. In rapidly dividing cells, including the majority of human cancers, cells bypass this growth limit through telomerase-catalyzed maintenance of telomere length. The dynamic properties of telomeres and telomerase render them difficult to study using ensemble biochemical and structural techniques...
March 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28372542/the-depletion-of-pinx1-involved-in-the-tumorigenesis-of-non-small-cell-lung-cancer-promotes-cell-proliferation-via-p15-cyclin-d1-pathway
#14
Xiao-Peng Tian, Xiao-Han Jin, Mei Li, Wei-Juan Huang, Dan Xie, Jia-Xing Zhang
BACKGROUND: The telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor. However, the clinical and biological significance of PinX1 in human non-small cell lung cancer (NSCLC) is unclear. METHODS: PinX1 gene/expression pattern and its association with NSCLC patient survival were analyzed in cBioportal Web resource and two cohorts of NSCLC samples. A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on NSCLC cells proliferation and underlying mechanisms...
April 4, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28369633/mutations-in-xlf-nhej1-cernunnos-gene-results-in-downregulation-of-telomerase-genes-expression-and-telomere-shortening
#15
Jaime Carrillo, Oriol Calvete, Laura Pintado Berninches, Cristina Manguan-García, Julian Sevilla Navarro, Elena G Arias-Salgado, Leandro Sastre, Guillermo Guenechea, Eduardo López Granados, Jean-Pierre de Villartay, Patrick Revy, Javier Benitez, Rosario Perona
NHEJ1-Patients develop severe progressive lymphocytopenia and premature aging of hematopoietic stem cells (HSCs) at a young age. Here we show, a patient with a homozygous-NHEJ1 mutation identified by whole exome-sequencing that developed severe pancytopenia and bone marrow aplasia correlating with the presence of short telomeres. The mutation resulted in a truncated protein. In an attempt to identify the mechanism behind the short telomere phenotype found in the NHEJ1-patient we downregulated NHEJ1 expression in 293T and CD34+cells...
March 24, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28366536/the-human-ctc1-stn1-ten1-complex-regulates-telomere-maintenance-in-alt-cancer-cells
#16
Chenhui Huang, Pingping Jia, Megan Chastain, Olga Shiva, Weihang Chai
Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle...
March 30, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28347991/patients-with-gout-have-short-telomeres-compared-with-healthy-participants-association-of-telomere-length-with-flare-frequency-and-cardiovascular-disease-in-gout
#17
N Vazirpanah, L B E Kienhorst, E Van Lochem, C Wichers, M Rossato, P G Shiels, N Dalbeth, L K Stamp, T R Merriman, M Janssen, T R D J Radstake, J Ca Broen
AIM AND BACKGROUND: Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout. METHODS: We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New Zealand...
March 27, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28343765/human-cardiac-progenitor-cells-with-regenerative-potential-can-be-isolated-and-characterized-from-3d-electro-anatomic-guided-endomyocardial-biopsies
#18
Domenico D'Amario, Antonio Maria Leone, Maria Lucia Narducci, Costantino Smaldone, Dalgisio Lecis, Frediano Inzani, Marco Luciani, Andrea Siracusano, Federica La Neve, Melissa Manchi, Gemma Pelargonio, Francesco Perna, Piergiorgio Bruno, Massimo Massetti, Dario Pitocco, Donato Cappetta, Grazia Esposito, Konrad Urbanek, Antonella De Angelis, Francesco Rossi, Roberto Piacentini, Giulia Angelini, Domenica Donatella Li Puma, Claudio Grassi, Elisa De Paolis, Ettore Capoluongo, Valentina Silvestri, Biagio Merlino, Riccardo Marano, Filippo Crea
AIMS: In the present study, we aimed to develop a percutaneous approach and a reproducible methodology for the isolation and expansion of Cardiac Progenitor Cells (CPCs) from EndoMyocardial Biopsies (EMB) in vivo. Moreover, in an animal model of non-ischemic heart failure (HF), we would like to test whether CPCs obtained by this methodology may engraft the myocardium and differentiate. METHODS AND RESULTS: EMB were obtained using a preformed sheath and a disposable bioptome, advanced via right femoral vein in 12 healthy mini pigs, to the right ventricle...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28342451/tert-promoter-mutations-in-telomere-biology
#19
REVIEW
Barbara Heidenreich, Rajiv Kumar
Telomere repeats at chromosomal ends, critical to genome integrity, are maintained through an elaborate network of proteins and pathways. Shelterin complex proteins shield telomeres from induction of DNA damage response to overcome end protection problem. A specialized ribonucleic protein, telomerase, maintains telomere homeostasis through repeat addition to counter intrinsic shortcomings of DNA replication that leads to gradual sequence shortening in successive mitoses. The biogenesis and recruitment of telomerase composed of telomerase reverse transcriptase (TERT) subunit and an RNA component, takes place through the intricate machinery that involves an elaborate number of molecules...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28337032/drosophila-dyskerin-is-required-for-somatic-stem-cell-homeostasis
#20
Rosario Vicidomini, Arianna Petrizzo, Annamaria di Giovanni, Laura Cassese, Antonella Anna Lombardi, Caterina Pragliola, Maria Furia
Drosophila represents an excellent model to dissect the roles played by the evolutionary conserved family of eukaryotic dyskerins. These multifunctional proteins are involved in the formation of H/ACA snoRNP and telomerase complexes, both involved in essential cellular tasks. Since fly telomere integrity is guaranteed by a different mechanism, we used this organism to investigate the specific role played by dyskerin in somatic stem cell maintenance. To this aim, we focussed on Drosophila midgut, a hierarchically organized and well characterized model for stemness analysis...
March 23, 2017: Scientific Reports
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