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https://www.readbyqxmd.com/read/29775593/structure-of-telomerase-with-telomeric-dna
#1
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/29774655/ctc1-stn1-coordinates-g-and-c-strand-synthesis-to-regulate-telomere-length
#2
Peili Gu, Shuting Jia, Taylor Takasugi, Eric Smith, Jayakrishnan Nandakumar, Eric Hendrickson, Sandy Chang
Coats plus (CP) is a rare autosomal recessive disorder caused by mutations in CTC1, a component of the CST (CTC1, STN1, and TEN1) complex important for telomere length maintenance. The molecular basis of how CP mutations impact upon telomere length remains unclear. The CP CTC1L1142H mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and RPE cells to demonstrate that CTC1:STN1 interaction is required to repress telomerase activity...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29774234/the-fission-yeast-stn1-ten1-complex-limits-telomerase-activity-via-its-sumo-interacting-motif-and-promotes-telomeres-replication
#3
Samah Matmati, Mélina Vaurs, José M Escandell, Laetitia Maestroni, Toru M Nakamura, Miguel G Ferreira, Vincent Géli, Stéphane Coulon
Mammalian CST (CTC1-STN1-TEN1) complex fulfills numerous functions including rescue of the stalled replication forks and termination of telomerase action. In fission yeast lacking the CTC1 ortholog, the Stn1-Ten1 complex restricts telomerase action via its sumoylation-mediated interaction with Tpz1TPP1 . We identify a small ubiquitin-like modifier (SUMO)-interacting motif (SIM) in the carboxyl-terminal part of Stn1 and show that this domain is crucial for SUMO and Tpz1-SUMO interactions. Point mutations in the SIM (Stn1-226) lead to telomere elongation, impair Stn1-Ten1 recruitment to telomeres, and enhance telomerase binding, revealing that Stn1 SIM domain contributes to the inhibition of telomerase activity at chromosome ends...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29773796/high-resolution-afm-structure-of-dna-g-wires-in-aqueous-solution
#4
Krishnashish Bose, Christopher J Lech, Brahim Heddi, Anh Tuân Phan
We investigate the self-assembly of short pieces of the Tetrahymena telomeric DNA sequence d[G4 T2 G4 ] in physiologically relevant aqueous solution using atomic force microscopy (AFM). Wire-like structures (G-wires) of 3.0 nm height with well-defined surface periodic features were observed. Analysis of high-resolution AFM images allowed their classification based on the periodicity of these features. A major species is identified with periodic features of 4.3 nm displaying left-handed ridges or zigzag features on the molecular surface...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773556/prdx1-and-mth1-cooperate-to-prevent-ros-mediated-inhibition-of-telomerase
#5
Wareed Ahmed, Joachim Lingner
Telomerase counteracts telomere shortening and cellular senescence in germ, stem, and cancer cells by adding repetitive DNA sequences to the ends of chromosomes. Telomeres are susceptible to damage by reactive oxygen species (ROS), but the consequences of oxidation of telomeres on telomere length and the mechanisms that protect from ROS-mediated telomere damage are not well understood. In particular, 8-oxoguanine nucleotides at 3' ends of telomeric substrates inhibit telomerase in vitro, whereas, at internal positions, they suppress G-quadruplex formation and were therefore proposed to promote telomerase activity...
May 17, 2018: Genes & Development
https://www.readbyqxmd.com/read/29771920/maternal-human-telomerase-reverse-transcriptase-variants-are-associated-with-preterm-labor-and-preterm-premature-rupture-of-membranes
#6
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/29771780/biomarkers-of-aging-in-hiv-infected-children-on-suppressive-antiretroviral-therapy
#7
Stephanie Shiau, Renate Strehlau, Jing Shen, Avy Violari, Faeezah Patel, Afaaf Liberty, Marc Foca, Shuang Wang, Mary Beth Terry, Michael T Yin, Ashraf Coovadia, Elaine J Abrams, Stephen M Arpadi, Louise Kuhn
BACKGROUND: Data on accelerated aging in HIV-infected children are limited. In this study we assess two biomarkers of aging - telomere length and DNA methylation (DNAm) age - in a cohort of early-treated HIV-infected children and compare these aging biomarkers to HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children. SETTING: Cross-sectional study of 120 HIV-infected, 33 HEU, and 25 HUU children enrolled in a cohort study in Johannesburg, South Africa...
April 27, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29771410/g-quadruplex-antibody-attenuates-human-gastric-cancer-cell-proliferation-and-promotes-apoptosis-through-htert-telomerase-pathway
#8
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/29770205/beginning-at-the-ends-telomeres-and-human-disease
#9
REVIEW
Sharon A Savage
Studies of rare and common illnesses have led to remarkable progress in the understanding of the role of telomeres (nucleoprotein complexes at chromosome ends essential for chromosomal integrity) in human disease. Telomere biology disorders encompass a growing spectrum of conditions caused by rare pathogenic germline variants in genes encoding essential aspects of telomere function. Dyskeratosis congenita, a disorder at the severe end of this spectrum, typically presents in childhood with the classic triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia, accompanied by a very high risk of bone marrow failure, cancer, pulmonary fibrosis, and other medical problems...
2018: F1000Research
https://www.readbyqxmd.com/read/29769793/a-marker-of-biological-ageing-predicts-adult-risk-preference-in-european-starlings-sturnus-vulgaris
#10
Clare Andrews, Daniel Nettle, Sophie Reichert, Tom Bedford, Pat Monaghan, Melissa Bateson
Why are some individuals more prone to gamble than others? Animals often show preferences between 2 foraging options with the same mean reward but different degrees of variability in the reward, and such risk preferences vary between individuals. Previous attempts to explain variation in risk preference have focused on energy budgets, but with limited empirical support. Here, we consider whether biological ageing, which affects mortality and residual reproductive value, predicts risk preference. We studied a cohort of European starlings ( Sturnus vulgaris ) in which we had previously measured developmental erythrocyte telomere attrition, an established integrative biomarker of biological ageing...
May 2018: Behavioral Ecology: Official Journal of the International Society for Behavioral Ecology
https://www.readbyqxmd.com/read/29768208/the-cst-complex-mediates-end-protection-at-double-strand-breaks-and-promotes-parp-inhibitor-sensitivity-in-brca1-deficient-cells
#11
Marco Barazas, Stefano Annunziato, Stephen J Pettitt, Inge de Krijger, Hind Ghezraoui, Stefan J Roobol, Catrin Lutz, Jessica Frankum, Fei Fei Song, Rachel Brough, Bastiaan Evers, Ewa Gogola, Jinhyuk Bhin, Marieke van de Ven, Dik C van Gent, Jacqueline J L Jacobs, Ross Chapman, Christopher J Lord, Jos Jonkers, Sven Rottenberg
Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration of BRCA1-independent homologous recombination through loss of factors such as 53BP1, RIF1, and REV7/MAD2L2, which inhibit end resection of DNA double-strand breaks (DSBs). To identify additional factors involved in this process, we performed CRISPR/SpCas9-based loss-of-function screens and selected for factors that confer PARP inhibitor (PARPi) resistance in BRCA1-deficient cells...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29765418/isolation-and-characterisation-of-mesenchymal-stem-cells-from-rat-bone-marrow-and-the-endosteal-niche-a-comparative-study
#12
Norhayati Yusop, Paul Battersby, Amr Alraies, Alastair J Sloan, Ryan Moseley, Rachel J Waddington
Within bone, mesenchymal stromal cells (MSCs) exist within the bone marrow stroma (BM-MSC) and the endosteal niche, as cells lining compact bone (CB-MSCs). This study isolated and characterised heterogeneous MSC populations from each niche and subsequently investigated the effects of extensive cell expansion, analysing population doublings (PDs)/cellular senescence, colony-forming efficiencies (CFEs), MSC cell marker expression, and osteogenic/adipogenic differentiation. CB-MSCs and BM-MSCs demonstrated similar morphologies and PDs, reaching 100 PDs...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29761887/telomere-length-and-genetic-variations-affecting-telomere-length-as-biomarkers-for-facial-regeneration-with-platelet-rich-fibrin-based-on-the-low-speed-centrifugation-concept
#13
Cleopatra Nacopoulos, Kalliopi Gkouskou, Dimitrios Karypidis, Ioannis Vlastos, Anna-Maria Vesala, Joseph Choukroun, Richard J Miron, Emmanuel Prokopakis
BACKGROUND: Platelet-Rich Fibrin (PRF), a fibrin matrix produced by single blood centrifugation that contains leukocytes, platelets, and growth factors, is increasingly being utilized for facial regeneration purposes. However, our understanding of the involved pathophysiological mechanisms affecting regeneration is limited and current protocols require better optimization. Biomarkers that are related to skin aging such as telomere length (TL) have been proposed as a mean to analyze patients' stratification...
May 15, 2018: Journal of Cosmetic Dermatology
https://www.readbyqxmd.com/read/29761675/telomere-length-aggregates-and-capture-in-cirrhosis
#14
Ido Laish, Amir Mari, Batya Mannasse, Ruth Hadary, Fred Meir Konikoff, Aliza Amiel, Yona Kitay-Cohen
BACKGROUND: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules. OBJECTIVES: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology. METHODS: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV)...
May 2018: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/29760601/tumor-cell-accelerated-senescence-is-associated-with-dna-pkcs-status-and-telomere-dysfunction-induced-by-radiation
#15
Miaomiao Zhang, Xiaopeng Guo, Yue Gao, Dong Lu, Wenjian Li
Whether telomere structure integrity is related to radiosensitivity is not well investigated thus far. In this study, we investigated the relation between telomere instability and radiation-induced accelerated senescence. Partial knockdown of DNA-dependent catalytic subunit of protein kinase (DNA-PKcs) in human breast cancer cell line MCF-7 was established by small interfering RNA. Radiosensitivity of control and DNA-PKcs knockdown MCF-7 cells was analyzed by clonogenetic assay. Cell growth was measured by real-time cell electronic sensing...
April 2018: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/29759988/transient-telomerase-inhibition-with-imetelstat-impacts-dna-damage-signals-and-cell-cycle-kinetics
#16
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/29758336/grand-rounds-hepatic-manifestations-of-telomere-biology-disorders
#17
REVIEW
Mrinal M Patnaik, Patrick S Kamath, Douglas A Simonetto
Clinical Case A 51 year old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia (NRH) with no significant fibrosis or necroinflammatory activity...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29757967/epigenetics-of-subcellular-structure-functioning-in-the-origin-of-risk-or-resilience-to-comorbidity-of-neuropsychiatric-and-cardiometabolic-disorders
#18
REVIEW
Carlos Manuel Zapata-Martín Del Campo, Martín Martínez-Rosas, Verónica Guarner-Lans
Mechanisms controlling mitochondrial function, protein folding in the endoplasmic reticulum (ER) and nuclear processes such as telomere length and DNA repair may be subject to epigenetic cues that relate the genomic expression and environmental exposures in early stages of life. They may also be involved in the comorbid appearance of cardiometabolic (CMD) and neuropsychiatric disorders (NPD) during adulthood. Mitochondrial function and protein folding in the endoplasmic reticulum are associated with oxidative stress and elevated intracellular calcium levels and may also underlie the vulnerability for comorbid CMD and NPD...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29757418/associations-of-arsenic-exposure-with-telomere-length-and-na%C3%A3-ve-t-cells-in-childhood-a-birth-cohort-study
#19
Tania Mannan, Sultan Ahmed, Evana Akhtar, Khalid Bin Ahsan, Ahsanul Haq, Maria Kippler, Marie Vahter, Rubhana Raqib
There is limited knowledge of association between arsenic exposure and telomere length (TL) and signal joint T-cell receptor excision circle (sjTREC) that are potential biomarkers of immune senescence and disease susceptibility. We aimed to clarify whether long-term inorganic arsenic exposure influences TL and sjTRECs in childhood. Children born in a longitudinal mother-child cohort were followed-up at 4.5 (n=275) and 9 years (n=351) of age. Arsenic exposure was assessed by metabolite concentrations in urine (U-As) from mothers at gestational week 8 (prenatal) and their children at 4...
May 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29755986/implications-of-cellular-aging-in-cardiac-reprogramming
#20
Fabiana Passaro, Gianluca Testa
Aging is characterized by a chronic functional decline of organ systems which leads to tissue dysfunction over time, representing a risk factor for diseases development, including cardiovascular. The aging process occurring in the cardiovascular system involves heart and vessels at molecular and cellular level, with subsequent structural modifications and functional impairment. Several modifications involved in the aging process can be ascribed to cellular senescence, a biological response that limits the proliferation of damaged cells...
2018: Frontiers in Cardiovascular Medicine
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