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Telomere d

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
Z Schuss, K Tor, D Holcman
Can the cell's perception of time be expressed through the length of the shortest telomere? To address this question, we analyze an asymmetric random walk that models telomere length for each division that can decrease by a fixed length a or, if recognized by a polymerase, it increases by a fixed length b ≫ a. Our analysis of the model reveals two phases, first, a determinist drift of the length toward a quasi-equilibrium state, and second, persistence of the length near an attracting state for the majority of divisions...
May 9, 2018: Journal of Theoretical Biology
Carolyn M Bauer, Jessica L Graham, Mikus Abolins-Abols, Britt J Heidinger, Ellen D Ketterson, Timothy J Greives
Female vertebrates that breed earlier in the season generally have greater reproductive success. However, evidence suggests that breeding early may be costly, thus leading to the prediction that females with fewer future reproductive events will breed earlier in the season. While chronological age is a good indicator of remaining life span, telomere lengths may also be good biomarkers of longevity as they potentially reflect lifetime wear and tear (i.e., biological age). We examined whether variation in the timing of the first seasonal clutch was related to age and telomere length in female dark-eyed juncos (Junco hyemalis), predicting that older females and those with shorter telomeres would breed earlier...
June 2018: American Naturalist
Jinbo Zhu, Zhiqiang Yan, Weijun Zhou, Chuanbo Liu, Jin Wang, Erkang Wang
Thioflavin T (ThT) was once regarded to be a specific fluorescent probe for the human telomeric G-quadruplex, but more other kinds of DNA were found that can also bind to ThT in recent years. Herein, we focus on G-rich parallel-stranded DNA and utilize fluorescence, absorbance, circular dichroism and surface plasmon resonance spectroscopy to investigate its interaction with ThT. Pyrene label and molecular modelling are applied to unveil the binding mechanism. We find a new class of non-G-quadruplex G-rich parallel-stranded (ps) DNA with the sequence of TG(GA)n can bind to ThT and increase the fluorescence with an enhancement ability superior to G-quadruplex...
May 11, 2018: ACS Sensors
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
Xin D Gao, Li-Chun Tu, Aamir Mir, Tomás Rodriguez, Yuehe Ding, John Leszyk, Job Dekker, Scott A Shaffer, Lihua Julie Zhu, Scot A Wolfe, Erik J Sontheimer
Mapping proteomic composition at distinct genomic loci in living cells has been a long-standing challenge. Here we report that dCas9-APEX2 biotinylation at genomic elements by restricted spatial tagging (C-BERST) allows the rapid, unbiased mapping of proteomes near defined genomic loci, as demonstrated for telomeres and centromeres. C-BERST enables the high-throughput identification of proteins associated with specific sequences, thereby facilitating annotation of these factors and their roles.
May 7, 2018: Nature Methods
Cassiana Siebert, Tiago Marcon Dos Santos, Carolina Gessinger Bertó, Mariana Migliorini Parisi, Ritiéle Pinto Coelho, Vanusa Manfredini, Florencia M Barbé-Tuana, Angela T S Wyse
The aim of this study was to investigate the effect of ovariectomy (OVX), a surgical model of menopause, and/or vitamin D (VIT D) supplementation on oxidative status, DNA damage, and telomere length in hippocampus of rats at two ages. Ninety-day-old (adult) or 180-day-old (older) female Wistar rats were divided into four groups: SHAM, OVX, VIT D, and OVX + VIT D. Thirty days after OVX, rats were supplemented with VIT D (500 IU/kg) by gavage, for a period of 30 days. Results showed that OVX altered antioxidant enzymes, increasing the activities of catalase in adult rats and superoxide dismutase in older rats...
May 5, 2018: Neurotoxicity Research
Jia Ma, Yanru Guo, Jialei Hu, Yue Pan, Xia Qi, Huaxin Wang, Li Jia
The aging of many mammalian tissues is associated with loss of functional adult stem cells, especially bone marrow-derived mesenchymal stem cells (BMSCs). This study was aimed to analyze the biological effect of chick embryo (CE) and nutrient mixture (NM) on the BMSCs of aging rats. The aging rat model was established to be induced by D-galactose (500 mg/kg/d) for 90 days. Meanwhile, aging rats were fed with CE and NM in different dose manner by intragastric administration. At the end of the experimental period, serum was collected from rats and used for BMSCs culture...
May 4, 2018: Scientific Reports
Mariana G Tarragó, Claudia C S Chini, Karina S Kanamori, Gina M Warner, Ariel Caride, Guilherme C de Oliveira, Micaela Rud, Adrienne Samani, Kyaw Z Hein, Runqing Huang, Diana Jurk, Dong Seong Cho, James J Boslett, Jordan D Miller, Jay L Zweier, João F Passos, Jason D Doles, David J Becherer, Eduardo N Chini
Aging is characterized by the development of metabolic dysfunction and frailty. Recent studies show that a reduction in nicotinamide adenine dinucleotide (NAD+ ) is a key factor for the development of age-associated metabolic decline. We recently demonstrated that the NADase CD38 has a central role in age-related NAD+ decline. Here we show that a highly potent and specific thiazoloquin(az)olin(on)e CD38 inhibitor, 78c, reverses age-related NAD+ decline and improves several physiological and metabolic parameters of aging, including glucose tolerance, muscle function, exercise capacity, and cardiac function in mouse models of natural and accelerated aging...
May 1, 2018: Cell Metabolism
Tingting Ai, Qiufang Yang, You Lv, Yuqin Huang, Yuzhi Li, Jia Geng, Dan Xiao, Cuisong Zhou
The oxidative damage toxic property of G-quadruplex (G4), linked to neurodegenerative diseases, may arise from their ability to bind and oxidatively activate cellular hemin. However, there have been no precise studies on how telomeric G4 enhances the low intrinsic peroxidase activity of hemin. Herein, a label-free and nanopore-based strategy was developed to explore the enhancement mechanism of peroxidase activity of hemin induced by telomeric G4 (d(TTAGGG)n). The nanopore-based strategy demonstrated that there were simultaneously two different binding modes of telomere G4 to hemin...
May 2, 2018: Chemistry, An Asian Journal
Tim De Meyer, Sofie Bekaert, Marc L De Buyzere, Dirk D De Bacquer, Michel R Langlois, Nitin Shivappa, James R Hébert, Thierry C Gillebert, Ernst R Rietzschel, Inge Huybrechts
Telomere length is a prognostic biomarker for aging diseases. As it is unknown whether diet plays a role in these associations, we aimed to assess the impact of diet on telomere length. Moreover, given that telomere length is modulated by oxidative stress and inflammation, an additional goal was to evaluate whether the latter may mediate possible telomere - diet associations. Southern blot measured leukocyte telomere length and food frequency questionnaire data were compared for 2509 apparently healthy men and women (~35 to 55 years) from the Asklepios population...
April 25, 2018: Scientific Reports
Özgün Özer, Ian D Hickson
Oncogene activation during tumour development leads to changes in the DNA replication programme that enhance DNA replication stress. Certain regions of the human genome, such as common fragile sites and telomeres, are particularly sensitive to DNA replication stress due to their inherently 'difficult-to-replicate' nature. Indeed, it appears that these regions sometimes fail to complete DNA replication within the period of interphase when cells are exposed to DNA replication stress. Under these conditions, cells use a salvage pathway, termed 'mitotic DNA repair synthesis (MiDAS)', to complete DNA synthesis in the early stages of mitosis...
April 2018: Open Biology
P J Hohensinner, C Kaun, B Ebenbauer, M Hackl, S Demyanets, D Richter, M Prager, J Wojta, Gersina Rega-Kaun
BACKGROUND: Obesity is considered to be a major comorbidity. Obese patients suffer from an increased proinflammatory state associated with a premature aging phenotype including increased secretion of senescence-associated secretory proteins (SASP) and reduced telomere length. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that could modify the post-transcriptional process. Several studies have reported associations between miRNAs and metabolic unhealthy conditions. AIM: To determine if bariatric surgery and the resulting weight loss could reverse the premature aging phenotype...
April 25, 2018: Obesity Surgery
Philip M C Davy, D Craig Willcox, Michio Shimabukuro, Timothy A Donlon, Trevor Torigoe, Makoto Suzuki, Moritake Higa, Hiroaki Masuzaki, Masataka Sata, Randi Chen, Rachel Murkofsky, Brian J Morris, Eunjung Lim, Richard C Allsopp, Bradley J Willcox
FOXO3 is one of the most prominent genes demonstrating a consistently reproducible genetic association with human longevity. The mechanisms by which these individual gene variants confer greater organismal lifespan are not well understood. We assessed the effect of longevity-associated FOXO3 alleles on age-related leukocyte telomere dynamics in a cross-sectional study comprising of samples from 121 healthy Okinawan-Japanese donors aged 21-95 years. We found that telomere length for carriers of the longevity associated allele of FOXO3 single nucleotide polymorphism rs2802292 displayed no significant correlation with age, an effect that was most pronounced in older (>50) participants...
April 21, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Sébastien Fritz, Chris Hoze, Emmanuelle Rebours, Anne Barbat, Méline Bizard, Amanda Chamberlain, Clémentine Escouflaire, Christy Vander Jagt, Mekki Boussaha, Cécile Grohs, Aurélie Allais-Bonnet, Maëlle Philippe, Amélie Vallée, Yves Amigues, Benjamin J Hayes, Didier Boichard, Aurélien Capitan
Researching depletions in homozygous genotypes for specific haplotypes among the large cohorts of animals genotyped for genomic selection is a very efficient strategy to map recessive lethal mutations. In this study, by analyzing real or imputed Illumina BovineSNP50 (Illumina Inc., San Diego, CA) genotypes from more than 250,000 Holstein animals, we identified a new locus called HH6 showing significant negative effects on conception rate and nonreturn rate at 56 d in at-risk versus control mating. We fine-mapped this locus in a 1...
April 18, 2018: Journal of Dairy Science
Jennifer Anne Doherty, Laurie Grieshober, John R Houck, Matt J Barnett, Jean De Dieu Tapsoba, Mark D Thornquist, Ching-Yun Wang, Gary E Goodman, Chu Chen
BACKGROUND: Telomeres protect cells from genomic instability. We examined telomere length and lung cancer risk prospectively in heavy smokers. METHODS: In a nested case-control study with 709 cases and 1313 controls, conditional logistic regression was used to evaluate associations between telomere length (global, chromosome 5p, and 13q) and lung cancer risk by histotype, controlling for detailed smoking history. RESULTS: Risks of overall lung cancer and adenocarcinoma were suggestively elevated among individuals with telomere length in the longest tertile...
April 19, 2018: British Journal of Cancer
Maheshi Udugama, Elaine Sanij, Hsiao P J Voon, Jinbae Son, Linda Hii, Jeremy D Henson, F Lyn Chan, Fiona T M Chang, Yumei Liu, Richard B Pearson, Paul Kalitsis, Jeffrey R Mann, Philippe Collas, Ross D Hannan, Lee H Wong
ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors...
May 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
Özgün Özer, Rahul Bhowmick, Ying Liu, Ian D Hickson
Telomeres resemble common fragile sites (CFSs) in that they are difficult-to-replicate and exhibit fragility in mitosis in response to DNA replication stress. At CFSs, this fragility is associated with a delay in the completion of DNA replication until early mitosis, whereupon cells are proposed to switch to a RAD52-dependent form of break-induced replication. Here, we show that this mitotic DNA synthesis (MiDAS) is also a feature of human telomeres. Telomeric MiDAS is not restricted to those telomeres displaying overt fragility, and is a feature of a wide range of cell lines irrespective of whether their telomeres are maintained by telomerase or by the alternative lengthening of telomeres (ALT) mechanism...
March 23, 2018: Oncotarget
Thomas J Mitchell, Samra Turajlic, Andrew Rowan, David Nicol, James H R Farmery, Tim O'Brien, Inigo Martincorena, Patrick Tarpey, Nicos Angelopoulos, Lucy R Yates, Adam P Butler, Keiran Raine, Grant D Stewart, Ben Challacombe, Archana Fernando, Jose I Lopez, Steve Hazell, Ashish Chandra, Simon Chowdhury, Sarah Rudman, Aspasia Soultati, Gordon Stamp, Nicos Fotiadis, Lisa Pickering, Lewis Au, Lavinia Spain, Joanna Lynch, Mark Stares, Jon Teague, Francesco Maura, David C Wedge, Stuart Horswell, Tim Chambers, Kevin Litchfield, Hang Xu, Aengus Stewart, Reza Elaidi, Stéphane Oudard, Nicholas McGranahan, Istvan Csabai, Martin Gore, P Andrew Futreal, James Larkin, Andy G Lynch, Zoltan Szallasi, Charles Swanton, Peter J Campbell
Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis...
April 4, 2018: Cell
Jason J Liu, Elizabeth K Cahoon, Martha S Linet, Mark P Little, Casey L Dagnall, Herbert Higson, Sharon A Savage, D Michal Freedman
No abstract text is available yet for this article.
April 2018: British Journal of Nutrition
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