2,336 results match your criteria telomeres structures

Structures of telomerase at several steps of telomere repeat synthesis.

Nature 2021 May 12. Epub 2021 May 12.

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.

Telomerase is unique among the reverse transcriptases in containing a noncoding RNA (known as telomerase RNA (TER)) that includes a short template that is used for the processive synthesis of G-rich telomeric DNA repeats at the 3' ends of most eukaryotic chromosomes. Telomerase maintains genomic integrity, and its activity or dysregulation are critical determinants of human longevity, stem cell renewal and cancer progression. Previous cryo-electron microscopy structures have established the general architecture, protein components and stoichiometries of Tetrahymena and human telomerase, but our understandings of the details of DNA-protein and RNA-protein interactions and of the mechanisms and recruitment involved remain limited. Read More

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Beyond small molecules: targeting G-quadruplex structures with oligonucleotides and their analogues.

Nucleic Acids Res 2021 May 12. Epub 2021 May 12.

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

G-Quadruplexes (G4s) are widely studied secondary DNA/RNA structures, naturally occurring when G-rich sequences are present. The strategic localization of G4s in genome areas of crucial importance, such as proto-oncogenes and telomeres, entails fundamental implications in terms of gene expression regulation and other important biological processes. Although thousands of small molecules capable to induce G4 stabilization have been reported over the past 20 years, approaches based on the hybridization of a synthetic probe, allowing sequence-specific G4-recognition and targeting are still rather limited. Read More

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Cell-based model systems for genome instability: Dissecting the mechanistic basis of chromothripsis in cancer.

Int J Cancer 2021 May 1. Epub 2021 May 1.

Group Genome Instability in Tumors, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Chromothripsis is a form of genomic instability that was shown to play a major role in cancer. Beyond cancer, this type of catastrophic event is also involved in germline structural variation, genome mosaicism in somatic tissues, infertility, mental retardation, congenital malformations and reproductive development in plants. Several assays have been developed to model chromothripsis in vitro and to dissect the mechanistic basis of this phenomenon. Read More

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Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model.

Cells 2021 Apr 14;10(4). Epub 2021 Apr 14.

School of Biological Sciences & Institute for Global Food Security, Queens University Belfast, Belfast BT9 5DL, UK.

The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. Read More

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Telomere Replication: Solving Multiple End Replication Problems.

Front Cell Dev Biol 2021 1;9:668171. Epub 2021 Apr 1.

Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Cancer Research Pavilion, Université de Sherbrooke, Sherbrooke, QC, Canada.

Eukaryotic genomes are highly complex and divided into linear chromosomes that require end protection from unwarranted fusions, recombination, and degradation in order to maintain genomic stability. This is accomplished through the conserved specialized nucleoprotein structure of telomeres. Due to the repetitive nature of telomeric DNA, and the unusual terminal structure, namely a protruding single stranded 3' DNA end, completing telomeric DNA replication in a timely and efficient manner is a challenge. Read More

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2'-Fluoro-arabinonucleic Acid (FANA): A Versatile Tool for Probing Biomolecular Interactions.

Acc Chem Res 2021 May 16;54(9):2287-2297. Epub 2021 Apr 16.

Department of Chemistry, McGill University, Montreal, Quebec H3A 0B8, Canada.

ConspectusThis Account highlights the structural features that render 2'-deoxy-2'-fluoro-arabinonucleic acid (FANA) an ideal tool for mimicking DNA secondary structures and probing biomolecular interactions relevant to chemical biology.The high binding affinity of FANA to DNA and RNA has had implications in therapeutics. FANA can hybridize to complementary RNA, resulting in a predominant A-form helix stabilized by a network of 2'F-H8(purine) pseudohydrogen bonding interactions. Read More

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Crystal structures of N-terminally truncated telomerase reverse transcriptase from fungi‡.

Nucleic Acids Res 2021 May;49(8):4768-4781

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China.

Telomerase plays critical roles in cellular aging, in the emergence and/or development of cancer, and in the capacity for stem-cell renewal, consists of a catalytic telomerase reverse transcriptase (TERT) and a template-encoding RNA (TER). TERs from diverse organisms contain two conserved structural elements: the template-pseudoknot (T-PK) and a helical three-way junction (TWJ). Species-specific features of the structure and function of telomerase make obtaining a more in-depth understanding of the molecular mechanism of telomerase particularly important. Read More

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Interplay between RNA Viruses and Promyelocytic Leukemia Nuclear Bodies.

Vet Sci 2021 Mar 31;8(4). Epub 2021 Mar 31.

Department of Animal and Food and Sciences, University of Delaware, Newark, DE 19716, USA.

Promyelocytic leukemia nuclear bodies (PML NBs) are nuclear membrane-less sub structures that play a critical role in diverse cellular pathways including cell proliferation, DNA damage, apoptosis, transcriptional regulation, stem cell renewal, alternative lengthening of telomeres, chromatin organization, epigenetic regulation, protein turnover, autophagy, intrinsic and innate antiviral immunity. While intrinsic and innate immune functions of PML NBs or PML NB core proteins are well defined in the context of nuclear replicating DNA viruses, several studies also confirm their substantial roles in the context of RNA viruses. In the present review, antiviral activities of PML NBs or its core proteins on diverse RNA viruses that replicate in cytoplasm or the nucleus were discussed. Read More

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Investigation of the Interaction of Human Origin Recognition Complex Subunit 1 with G-Quadruplex DNAs of Human Promoter and Telomere Regions.

Int J Mol Sci 2021 Mar 27;22(7). Epub 2021 Mar 27.

Institute of Advanced Energy, Kyoto University, Kyoto 611-0011, Japan.

Origin recognition complex (ORC) binds to replication origins in eukaryotic DNAs and plays an important role in replication. Although yeast ORC is known to sequence-specifically bind to a replication origin, how human ORC recognizes a replication origin remains unknown. Previous genome-wide studies revealed that guanine (G)-rich sequences, potentially forming G-quadruplex (G4) structures, are present in most replication origins in human cells. Read More

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Cation competition and recruitment around the c-kit1 G-quadruplex using polarizable simulations.

Biophys J 2021 Mar 29. Epub 2021 Mar 29.

Department of Biochemistry, Virginia Tech, Blacksburg, Virginia; Center for Drug Discovery, Virginia Tech, Blacksburg, Virginia. Electronic address:

Nucleic acid-ion interactions are fundamentally important to the physical, energetic, and conformational properties of DNA and RNA. These interactions help fold and stabilize highly ordered secondary and tertiary structures, such as G-quadruplexes (GQs), which are functionally relevant in telomeres, replication initiation sites, and promoter sequences. The c-kit proto-oncogene encodes for a receptor tyrosine kinase and is linked to gastrointestinal stromal tumors, mast cell disease, and leukemia. Read More

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The regulation of the DNA damage response at telomeres: focus on kinases.

Biochem Soc Trans 2021 Apr;49(2):933-943

Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, Milano 20126, Italy.

The natural ends of linear chromosomes resemble those of accidental double-strand breaks (DSBs). DSBs induce a multifaceted cellular response that promotes the repair of lesions and slows down cell cycle progression. This response is not elicited at chromosome ends, which are organized in nucleoprotein structures called telomeres. Read More

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WALTER: an easy way to online evaluate telomere lengths from terminal restriction fragment analysis.

BMC Bioinformatics 2021 Mar 22;22(1):145. Epub 2021 Mar 22.

Mendel Centre for Plant Genomics and Proteomics, Central European Institute of Technology (CEITEC), Masaryk University, 625 00, Brno, Czech Republic.

Background: Telomeres, nucleoprotein structures comprising short tandem repeats and delimiting the ends of linear eukaryotic chromosomes, play an important role in the maintenance of genome stability. Therefore, the determination of the length of telomeres is of high importance for many studies. Over the last years, new methods for the analysis of the length of telomeres have been developed, including those based on PCR or analysis of NGS data. Read More

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Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci.

J Vis Exp 2021 03 4(169). Epub 2021 Mar 4.

Biosciences, Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire.

The genome is associated with several structures inside cell nuclei, in order to regulate its activity and anchor it in specific locations. These structures are collectively known as the nucleoskeleton and include the nuclear lamina, the nucleoli, and nuclear bodies. Although many variants of fluorescence in situ hybridization (FISH) exist to study the genome and its organization, these are often limited by resolution and provide insufficient information on the genome's association with nuclear structures. Read More

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Fluorescence microscopy methods for examining telomeres during cell aging.

Ageing Res Rev 2021 Mar 17;68:101320. Epub 2021 Mar 17.

Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Calgary, Alberta, T2N 4N1, Canada; Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. Electronic address:

Telomeres are protective structures, composed of nucleic acids and a complex protein mixture, located at the end of the chromosomes. They play an important role in preventing genomic instability and ensuring cell health. Defects in telomere integrity result in cell dysfunction and the development of diseases, including neurodegenerative disorders, cancer and premature aging syndromes, among others. Read More

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The Impact of Gastric Bypass on Telomere Length and Shelterin Complex Gene Expression: 6 Months Prospective Study.

Obes Surg 2021 Jun 18;31(6):2599-2606. Epub 2021 Mar 18.

Laboratory of Nutrigenomics Studies, Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.

Background: Telomeres are structures located at the ends of chromosomes associated with a protein complex, known as the shelterin complex. In individuals with obesity, excess adipose tissue plays a key role in inducing a chronic and systemic inflammatory state, which can cause TL shortening. In this context, bariatric surgery is one of the most effective treatment modalities in improving metabolic control. Read More

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Genome stability is guarded by yeast Rtt105 through multiple mechanisms.

Genetics 2021 Feb;217(2)

CNRS UMR7258, INSERM U1068, Aix-Marseille Université UM105, Institut Paoli-Calmettes, CRCM, Marseille, France.

Ty1 mobile DNA element is the most abundant and mutagenic retrotransposon present in the genome of the budding yeast Saccharomyces cerevisiae. Protein regulator of Ty1 transposition 105 (Rtt105) associates with large subunit of RPA and facilitates its loading onto a single-stranded DNA at replication forks. Here, we dissect the role of RTT105 in the maintenance of genome stability under normal conditions and upon various replication stresses through multiple genetic analyses. Read More

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February 2021

Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus.

Genetics 2021 Feb;217(2)

Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.

Drosophila telomeres have been maintained by three families of active transposable elements (TEs), HeT-A, TAHRE, and TART, collectively referred to as HTTs, for tens of millions of years, which contrasts with an unusually high degree of HTT interspecific variation. While the impacts of conflict and domestication are often invoked to explain HTT variation, the telomeres are unstable structures such that neutral mutational processes and evolutionary tradeoffs may also drive HTT evolution. We leveraged population genomic data to analyze nearly 10,000 HTT insertions in 85  Drosophila melanogaster genomes and compared their variation to other more typical TE families. Read More

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February 2021

Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites.

Front Cell Infect Microbiol 2021 26;11:612656. Epub 2021 Feb 26.

Department of Biomedical and Health Sciences, College of Nursing and Health Sciences, University of Vermont, Burlington, VT, United States.

Human herpesvirus -6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes. Viral integration can occur in several cell types, including germinal cells, resulting in individuals that harbor the viral genome in every cell of their body. The integrated genome is efficiently silenced but can sporadically reactivate resulting in various clinical symptoms. Read More

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February 2021

Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening.

Nat Commun 2021 03 12;12(1):1626. Epub 2021 Mar 12.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA.

Minichromosome maintenance protein 10 (MCM10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 variants in patients with distinctive, but overlapping, clinical phenotypes: natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) with hypoplasia of the spleen and thymus. To understand the mechanism of MCM10-associated disease, we modeled these variants in human cell lines. Read More

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ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells.

Nat Commun 2021 03 12;12(1):1654. Epub 2021 Mar 12.

The Wistar Institute, Philadelphia, PA, USA.

ADAR1 is involved in adenosine-to-inosine RNA editing. The cytoplasmic ADAR1p150 edits 3'UTR double-stranded RNAs and thereby suppresses induction of interferons. Loss of this ADAR1p150 function underlies the embryonic lethality of Adar1 null mice, pathogenesis of the severe autoimmune disease Aicardi-Goutières syndrome, and the resistance developed in cancers to immune checkpoint blockade. Read More

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Interrogating accessibility of telomeric sequences with FRET-PAINT: evidence for length-dependent telomere compaction.

Nucleic Acids Res 2021 04;49(6):3371-3380

Department of Physics, Kent State University, Kent, OH 44242, USA.

Single-stranded telomeric overhangs are ∼200 nucleotides long and can form tandem G-quadruplex (GQ) structures, which reduce their accessibility to nucleases and proteins that activate DNA damage response. Whether these tandem GQs further stack to form compact superstructures, which may provide better protection for longer telomeres, is not known. We report single-molecule measurements where the accessibility of 24-144 nucleotide long human telomeric DNA molecules is interrogated by a short PNA molecule that is complementary to a single GGGTTA repeat, as implemented in the FRET-PAINT method. Read More

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Frustrated folding of guanine quadruplexes in telomeric DNA.

Nucleic Acids Res 2021 04;49(6):3063-3076

Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, H3A 0B8, Canada.

Human chromosomes terminate in long, single-stranded, DNA overhangs of the repetitive sequence (TTAGGG)n. Sets of four adjacent TTAGGG repeats can fold into guanine quadruplexes (GQ), four-stranded structures that are implicated in telomere maintenance and cell immortalization and are targets in cancer therapy. Isolated GQs have been studied in detail, however much less is known about folding in long repeat sequences. Read More

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Long-read sequencing and de novo genome assemblies reveal complex chromosome end structures caused by telomere dysfunction at the single nucleotide level.

Nucleic Acids Res 2021 04;49(6):3338-3353

Department of Biological Sciences, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea.

Karyotype change and subsequent evolution is triggered by chromosome fusion and rearrangement events, which often occur when telomeres become dysfunctional. Telomeres protect linear chromosome ends from DNA damage responses (DDRs), and telomere dysfunction may result in genome instability. However, the complex chromosome end structures and the other possible consequences of telomere dysfunction have rarely been resolved at the nucleotide level due to the lack of the high-throughput methods needed to analyse these highly repetitive regions. Read More

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G-Quadruplex Structures Colocalize with Transcription Factories and Nuclear Speckles Surrounded by Acetylated and Dimethylated Histones H3.

Int J Mol Sci 2021 Feb 17;22(4). Epub 2021 Feb 17.

Institute of Biophysics of the Czech Academy of Sciences, Department of Molecular Cytology and Cytometry, Královopolská 135, 612 65 Brno, Czech Republic.

G-quadruplexes (G4s) are four-stranded helical structures that regulate several nuclear processes, including gene expression and telomere maintenance. We observed that G4s are located in GC-rich (euchromatin) regions and outside the fibrillarin-positive compartment of nucleoli. Genomic regions around G4s were preferentially H3K9 acetylated and H3K9 dimethylated, but H3K9me3 rarely decorated G4 structures. Read More

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February 2021

TA-65 does not increase telomere length during post-natal development in house sparrow chicks (Passer domesticus).

J Exp Zool A Ecol Integr Physiol 2021 Mar 2;335(3):359-366. Epub 2021 Mar 2.

Department of Biological Sciences, North Dakota State University, Fargo, North Dakota, USA.

Telomeres, protective caps at the end of chromosomes, are often positively related to lifespan and are thought to be an important mechanism of organismal aging. To better understand the casual relationships between telomere length and longevity, it is essential to be able to experimentally manipulate telomere dynamics (length and loss rate). Previous studies suggest that exposure to TA-65, an extract from the Chinese root Astragalus membranaceus, activates telomerase, lengthens telomeres, increases the growth of keratin-based structures, and boosts the immune system in adults. Read More

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G-quadruplexes: a promising target for cancer therapy.

Mol Cancer 2021 02 25;20(1):40. Epub 2021 Feb 25.

Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, 53127, Bonn, Germany.

DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). Read More

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February 2021

Resilience, pain, and the brain: Relationships differ by sociodemographics.

J Neurosci Res 2021 May 19;99(5):1207-1235. Epub 2021 Feb 19.

Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. Read More

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Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells.

Nat Commun 2021 02 17;12(1):1097. Epub 2021 Feb 17.

Department of Biological Sciences, Seoul National University, Seoul, Korea.

Telomeres are part of a highly refined system for maintaining the stability of linear chromosomes. Most telomeres rely on simple repetitive sequences and telomerase enzymes to protect chromosomal ends; however, in some species or telomerase-defective situations, an alternative lengthening of telomeres (ALT) mechanism is used. ALT mainly utilises recombination-based replication mechanisms and the constituents of ALT-based telomeres vary depending on models. Read More

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February 2021

G-quadruplex binding properties of a potent PARP-1 inhibitor derived from 7-azaindole-1-carboxamide.

Sci Rep 2021 Feb 16;11(1):3869. Epub 2021 Feb 16.

Department of Food, Environmental and Nutritional Sciences (DEFENS), University of Milan (Università Degli Studi Di Milano), Milan, Italy.

Poly ADP-ribose polymerases (PARP) are key proteins involved in DNA repair, maintenance as well as regulation of programmed cell death. For this reason they are important therapeutic targets for cancer treatment. Recent studies have revealed a close interplay between PARP1 recruitment and G-quadruplex stabilization, showing that PARP enzymes are activated upon treatment with a G4 ligand. Read More

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February 2021