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Telomere research

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https://www.readbyqxmd.com/read/28524432/solution-nmr-structure-of-a-ligand-hybrid-2-g-quadruplex-complex-reveals-rearrangements-that-affect-ligand-binding
#1
Julia Wirmer-Bartoschek, Lars Erik Bendel, Hendrik R A Jonker, J Tassilo Grün, Francesco Papi, Carla Bazzicalupi, Luigi Messori, Paola Gratteri, Harald Schwalbe
Telomeric G-quadruplexes have recently emerged as drug targets in cancer research. Herein, we present the first NMR structure of a telomeric DNA G-quadruplex that adopts the biologically relevant hybrid-2 conformation in a ligand-bound state. We solved the complex with a metalorganic gold(III) ligand that stabilizes G-quadruplexes. Analysis of the free and bound structures reveals structural changes in the capping region of the G-quadruplex. The ligand is sandwiched between one terminal G-tetrad and a flanking nucleotide...
May 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28521962/the-functional-roles-of-pml-nuclear-bodies-in-genome-maintenance
#2
REVIEW
Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan Kim
In the nucleus, there are several membraneless structures called nuclear bodies. Among them, promyelocytic leukemia nuclear bodies (PML-NBs) are involved in multiple genome maintenance pathways including the DNA damage response, DNA repair, telomere homeostasis, and p53-associated apoptosis. In response to DNA damage, PML-NBs are coalesced and divided by a fission mechanism, thus increasing their number. PML-NBs also play a role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Clinically, the dominant negative PML-RARα fusion protein expressed in acute promyelocytic leukemia (APL) inhibits the transactivation of downstream factors and disrupts PML function, revealing the tumor suppressor role of PML-NBs...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28500672/telomere-length-and-fetal-programming-a-review-of-recent-scientific-advances
#3
Valerie E Whiteman, Anjali Goswami, Hamisu M Salihu
We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication...
May 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28452859/tert-mediated-and-atrx-mediated-telomere-maintenance-and-neuroblastoma
#4
Xiao-Feng Duan, Qiang Zhao
Neuroblastomas (NB) are one of the most common extracranial solid tumors in children, and they frequently display high heterogeneity in the disease course. With ongoing research, more information regarding the genetic etiology and molecular mechanisms underlying these contrasting phenotypes is being uncovered. The proto-oncogene MYCN is amplified in approximately 20% of NB cases and is considered a indicator of poor prognosis and an indicator of high-risk NB. The poor prognosis of high risk NB is incompletely explained by MYCN amplification...
April 27, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28443517/1-3-4-oxadiazoles-as-telomerase-inhibitor-potential-anticancer-agents
#5
Shalini Bajaj, Partha Pratim Roy, Jagadish Singh
Cancer is a rapidly growing disease of current era which poses a major life threaten situation to human beings. Continuous research is going on in the direction to develop effective molecules for the treatment of the cancer. These efforts include searching of more active heterocyclic compounds possessing potential anti-cancer activity. The 1,3,4-Oxadiazole scaffold is a five member heterocyclic ring having versatile activities and created interest for synthetic organic and medicinal chemists for the designing of novel compounds having anti-cancer activity...
April 24, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28420806/the-association-of-occupational-metals-exposure-and-oxidative-damage-telomere-shortening-in-fitness-equipments-manufacturing-workers
#6
Jiunn-Liang Ko, Yu-Jung Cheng, Guan-Cen Liu, I-Lun Hsin, Hsiu-Ling Chen
The welding is the major working process in fitness equipment manufacturing industry, and International Agency for Research on Cancer has classified welding fumes as possibly carcinogenic to humans (Group 2B). The present study aimed to evaluate associations between the occupational exposure of metals and oxidative damage and telomere length shortening in workers involved in the manufacture of fitness equipment. The blood metal concentrations were monitored and malondialdehyde (MDA), alkaline Comet assay was determined as oxidative damage in 117 workers from two representative fitness equipment manufacturing plants...
April 14, 2017: Industrial Health
https://www.readbyqxmd.com/read/28410770/calcium-signaling-and-cellular-senescence
#7
REVIEW
Nadine Martin, David Bernard
Cellular senescence is a stable cell proliferation arrest induced by a variety of stresses including telomere shortening, oncogene activation and oxidative stress. This process plays a crucial role in many physiopathological contexts, especially during aging when cellular senescence favors development of age-related diseases, shortening lifespan. However, the molecular and cellular mechanisms controlling senescence are still a matter of active research. In the last decade, there has been emerging literature indicating a key involvement of calcium signaling in cellular senescence...
April 5, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28410238/physical-activity-and-telomere-length-impact-of-aging-and-potential-mechanisms-of-action
#8
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/28397798/telomere-length-in-newborns-is-related-to-maternal-stress-during-pregnancy
#9
T Send, M Gilles, V Codd, I A C Wolf, S Bardtke, F Streit, J Strohmaier, J Frank, D Schendel, M W Sütterlin, M Denniff, M Laucht, N J Samani, M Deuschle, M Rietschel, S H Witt
Telomere length (TL) is a marker of biological aging, and numerous studies have shown associations between TL and somatic or psychiatric disorders. Research also indicates an association between maternal stress during pregnancy and TL in the offspring. The present study investigated possible associations between TL and: (1) maternal perceived stress during pregnancy; (2) a maternal life-time history of psychiatric disorder (life-time PD); and (3) paternal age. TL was analysed in 319 newborns and 318 mothers from a predominantly Caucasian sample (n=273 Caucasian newborns and n=274 Causasian mothers)...
April 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28389255/relative-telomere-length-before-hematopoietic-cell-transplantation-and-outcome-after-unrelated-donor-hematopoietic-cell-transplantation-for-acute-leukemia
#10
Youjin Wang, Tao Wang, Casey Dagnall, Michael Haagenson, Stephen R Spellman, Belynda Hicks, Kristine Jones, Stephanie J Lee, Sharon A Savage, Shahinaz M Gadalla
Telomeres are tandem nucleotide repeats and a protein complex located at the end of the chromosomes maintaining genomic stability. Their potential as a predictive biomarker for outcomes after allogeneic hematopoietic cell transplant (HCT) in hematologic malignancies is still unclear. From the Center for International Blood and Marrow Transplant Research we randomly selected 536 acute leukemia patients from those who underwent myeloablative 8/8 HLA-matched unrelated donor HCT between 2005 and 2012 and who had an available pre-HCT blood sample in the repository...
April 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28375735/single-molecule-studies-of-telomeres-and-telomerase
#11
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/28374746/intracellular-hmgb1-as-a-novel-tumor-suppressor-of-pancreatic-cancer
#12
Rui Kang, Yangchun Xie, Qiuhong Zhang, Wen Hou, Qingping Jiang, Shan Zhu, Jinbao Liu, Dexing Zeng, Haichao Wang, David L Bartlett, Timothy R Billiar, Herbert J Zeh, Michael T Lotze, Daolin Tang
Pancreatic ductal adenocarcinoma (PDAC) driven by oncogenic K-Ras remains among the most lethal human cancers despite recent advances in modern medicine. The pathogenesis of PDAC is partly attributable to intrinsic chromosome instability and extrinsic inflammation activation. However, the molecular link between these two events in pancreatic tumorigenesis has not yet been fully established. Here, we show that intracellular high mobility group box 1 (HMGB1) remarkably suppresses oncogenic K-Ras-driven pancreatic tumorigenesis by inhibiting chromosome instability-mediated pro-inflammatory nucleosome release...
April 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28373169/telomere-length-and-neighborhood-circumstances-evaluating-biological-response-to-unfavorable-exposures
#13
EDITORIAL
Shannon M Lynch, Nandita Mitra, Krithika Ravichandran, Jonathan Mitchell, Elaine Spangler, Wenting Zhou, Electra D Paskett, Sarah Gehlert, Cecilia DeGraffinreid, Raymond Stowe, Tamara Dubowitz, Harold Riethman, Charles C Branas, M K Peek, Timothy R Rebbeck
Background: Multilevel frameworks suggest neighborhood circumstances influence biology; however, this relationship is not well studied. Telomere length (TL) shortening has been associated with individual-level and neighborhood-level exposures and disease and may provide insights into underlying biologic mechanisms linking neighborhood with biology. To support neighborhood-biology investigations, we sought to determine the independent effect of neighborhood exposures on TL using standard multilevel linear regression models and quantile regression, a nonlinear, social science method applicable for testing the biologic hypothesis that extremes of the TL distribution are related to poor outcomes...
April 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28349399/imaging-of-chromosome-dynamics-in-mouse-testis-tissue-by-immuno-fish
#14
Harry Scherthan
The mouse (Mus musculus) represents the central mammalian genetic model system for biomedical and developmental research. Mutant mouse models have provided important insights into chromosome dynamics during the complex meiotic differentiation program that compensates for the genome doubling at fertilization. Homologous chromosomes (homologues) undergo dynamic pairing and recombine during first meiotic prophase before they become partitioned into four haploid sets by two consecutive meiotic divisions that lack an intervening S-phase...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324509/human-telomeric-g-quadruplex-structures-and-g-quadruplex-interactive-compounds
#15
Clement Lin, Danzhou Yang
G-quadruplexes are noncanonical secondary structures formed in DNA sequences containing consecutive runs of guanines. It has been shown that the 3' G-rich single-stranded overhangs of human telomeres can form G-quadruplex structures, and the human telomeric DNA G-quadruplexes are considered attractive targets for anticancer drugs. G-quadruplex-interactive compounds have been shown to inhibit telomerase access as well as telomere capping. Nuclear magnetic resonance (NMR) spectroscopy is a powerful method in determining the G-quadruplex structures under physiologically relevant conditions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324502/telomeres-and-nextgen-co-fish-directional-genomic-hybridization-telo-dgh%C3%A2
#16
Miles J McKenna, Erin Robinson, Edwin H Goodwin, Michael N Cornforth, Susan M Bailey
The cytogenomics-based methodology of Directional Genomic Hybridization (dGH™) emerged from the concept of strand-specific hybridization, first made possible by Chromosome Orientation FISH (CO-FISH), the utility of which was demonstrated in a variety of early applications, often involving telomeres. Similar to standard whole chromosome painting (FISH), dGH™ is capable of identifying inter-chromosomal rearrangements (translocations between chromosomes), but its distinctive strength stems from its ability to detect intra-chromosomal rearrangements (inversions within chromosomes), and to do so at higher resolution than previously possible...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324500/analysis-of-yeast-telomerase-by-primer-extension-assays
#17
Min Hsu, Neal F Lue
Telomeres are specialized nucleoprotein structures located at eukaryotic chromosomal termini, which are required for chromosome stability and are maintained by a reverse transcriptase named telomerase. Budding yeast has served as an extremely useful model system for analyzing telomere maintenance because the organism offers a wide range of genetic and biochemical tools. Several milestones in telomerase research have been reached through investigation of the yeast system. For example, the consequence of telomerase loss was first characterized in the budding yeast Saccharomyces cerevisiae...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324495/telomere-length-analysis-by-quantitative-fluorescent-in-situ-hybridization-q-fish
#18
Isabelle Ourliac-Garnier, Arturo Londoño-Vallejo
Length is a functional parameter of telomeres, the nucleoprotein structures that protect chromosome ends. The availability of highly specific, high affinity probes for telomeric repeat sequences allowed the development of quantitative approaches aimed at measuring telomere length directly on chromosomes or in interphase nuclei. Here, we describe a general method for telomere quantitative FISH on metaphase chromosomes and discuss its most common applications in research.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324494/analysis-of-average-telomere-length-in-human-telomeric-protein-knockout-cells-generated-by-crispr-cas9
#19
Jun Xu, Zhou Songyang, Dan Liu, Hyeung Kim
Telomeres play an important role in ensuring the integrity of the genome. Telomere shortening can lead to loss of genetic information and trigger DNA damage responses. Cultured mammalian cells have served as critical model systems for studying the function of telomere binding proteins and telomerase. Tremendous heterogeneity can be observed both between species and within a single cell population. Recent advances in genome editing (such as the development of the CRISPR/Cas9 platform) have further enabled researchers to carry out loss-of-function analysis of how disrupting key players in telomere maintenance affects telomere length regulation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324493/introduction-to-telomeres-and-telomerase
#20
Zhou Songyang
Telomeres are ends of chromosomes that play an important part in the biology of eukaryotic cells. Continued optimization and development of technologies have enabled researchers to probe the mechanisms of telomere maintenance in ever expanding areas. A combination of molecular, genetic, proteomic, and biochemical approaches has revealed the complex and coordinated action of telomerase and telomere-associated proteins. The length and integrity of telomeres are maintained to prevent telomere dysfunction, which has been linked to senescence, aging, disease, and cancer...
2017: Methods in Molecular Biology
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