275 results match your criteria block telomere

Telomerase in Brain: The New Kid on the Block and Its Role in Neurodegenerative Diseases.

Biomedicines 2021 Apr 29;9(5). Epub 2021 Apr 29.

Biosciences Institute, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.

Telomerase is an enzyme that in its canonical function extends and maintains telomeres, the ends of chromosomes. This reverse transcriptase function is mainly important for dividing cells that shorten their telomeres continuously. However, there are a number of telomere-independent functions known for the telomerase protein TERT (Telomerase Reverse Transcriptase). Read More

View Article and Full-Text PDF

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

View Article and Full-Text PDF
February 2021

Cytokinesis-block micronucleus cytome (CBMN-CYT) assay biomarkers and telomere length analysis in relation to inorganic elements in individuals exposed to welding fumes.

Ecotoxicol Environ Saf 2021 Apr 9;212:111935. Epub 2021 Feb 9.

Departamento de Biofísica, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil. Electronic address:

During the welding activities many compounds are released, several of these cause oxidative stress and inflammation and some are considered carcinogenic, in fact the International Agency for Research on Cancer established that welding fumes are carcinogenic to humans. The aim of the present study was to analyze the cytotoxic and genotoxic potential of exposure to welding fumes and to determine concentrations of metals in blood and urine of occupationally exposed workers. We included 98 welders and 100 non-exposed individuals. Read More

View Article and Full-Text PDF

Designed Metal-ATCUN Derivatives: Redox- and Non-redox-Based Applications Relevant for Chemistry, Biology, and Medicine.

iScience 2020 Dec 10;23(12):101792. Epub 2020 Nov 10.

LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.

The designed "ATCUN" motif (amino-terminal copper and nickel binding site) is a replica of naturally occurring ATCUN site found in many proteins/peptides, and an attractive platform for multiple applications, which include nucleases, proteases, spectroscopic probes, imaging, and small molecule activation. ATCUN motifs are engineered at periphery by conjugation to recombinant proteins, peptides, fluorophores, or recognition domains through chemically or genetically, fulfilling the needs of various biological relevance and a wide range of practical usages. This chemistry has witnessed significant growth over the last few decades and several interesting ATCUN derivatives have been described. Read More

View Article and Full-Text PDF
December 2020

Replisome bypass of a protein-based R-loop block by Pif1.

Proc Natl Acad Sci U S A 2020 12 16;117(48):30354-30361. Epub 2020 Nov 16.

HHMI, Rockefeller University, New York, NY 10065;

Efficient and faithful replication of the genome is essential to maintain genome stability. Replication is carried out by a multiprotein complex called the replisome, which encounters numerous obstacles to its progression. Failure to bypass these obstacles results in genome instability and may facilitate errors leading to disease. Read More

View Article and Full-Text PDF
December 2020

Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial.

J Alzheimers Dis 2020 ;78(4):1509-1518

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

Background: Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial.

Objective: To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. Read More

View Article and Full-Text PDF
January 2020

Effect of plasma polyunsaturated fatty acid levels on leukocyte telomere lengths in the Singaporean Chinese population.

Nutr J 2020 10 30;19(1):119. Epub 2020 Oct 30.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore.

Background: Shorter telomere length (TL) has been associated with poor health behaviors, increased risks of chronic diseases and early mortality. Excessive shortening of telomere is a marker of accelerated aging and can be influenced by oxidative stress and nutritional deficiency. Plasma n6:n3 polyunsaturated fatty acid (PUFA) ratio may impact cell aging. Read More

View Article and Full-Text PDF
October 2020

Emerging roles of lamins and DNA damage repair mechanisms in ovarian cancer.

Biochem Soc Trans 2020 10;48(5):2317-2333

Saha Institute of Nuclear Physics, Kolkata; Homi Bhabha National Institute, Mumbai.

Lamins are type V intermediate filament proteins which are ubiquitously present in all metazoan cells providing a platform for binding of chromatin and related proteins, thereby serving a wide range of nuclear functions including DNA damage repair. Altered expression of lamins in different subtypes of cancer is evident from researches worldwide. But whether cancer is a consequence of this change or this change is a consequence of cancer is a matter of future investigation. Read More

View Article and Full-Text PDF
October 2020

Cytokinesis-Block Micronucleus Cytome Assay Evolution into a More Comprehensive Method to Measure Chromosomal Instability.

Michael Fenech

Genes (Basel) 2020 Oct 15;11(10). Epub 2020 Oct 15.

Genome Health Foundation, North Brighton, SA 5048, Australia.

This review describes the cytokinesis-block micronucleus (CBMN) cytome assay and its evolution into a molecular cytogenetic method of chromosomal instability (CIN). Micronuclei (MNi) originate from whole chromosomes or chromosome fragments that fail to segregate to the poles of the cell during mitosis. These lagging chromosomes are excluded from the daughter nuclei and are enveloped in their own membrane to form MNi. Read More

View Article and Full-Text PDF
October 2020

N-terminal modified cyclopeptidic mimetics of Apollo as inhibitors of TRF2.

Bioorg Med Chem Lett 2020 11 13;30(21):127401. Epub 2020 Jul 13.

Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Telomeric repeat binding factor 2 (TRF2) plays an important role in protecting telomeres from being recognized as DNA breaks. TRF2 performs its telomere protecting functions partially by recruiting a number of accessory proteins to telomeres through its TRF homology (TFRH) domain. Identification of small molecular compounds which can bind to the TRFH domain of TRF2 and block the interactions between TRF2 and its associated proteins is crucial for elucidating the molecular mechanisms of these protein-protein interactions. Read More

View Article and Full-Text PDF
November 2020

Endogenization and excision of human herpesvirus 6 in human genomes.

PLoS Genet 2020 08 10;16(8):e1008915. Epub 2020 Aug 10.

Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactivate into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. Read More

View Article and Full-Text PDF

The effects of aspirin and N-3 fatty acids on telomerase activity in adults with diabetes mellitus.

Nutr Metab Cardiovasc Dis 2020 09 25;30(10):1795-1799. Epub 2020 Jun 25.

Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; Cardiology Division, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address:

Type 2 Diabetes mellitus is associated with aging and shortened telomere length. Telomerase replaces lost telomeric repeats at the ends of chromosomes and is necessary for the replicative immortality of cells. Aspirin and the n3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are commonly used therapies in people with type 2 diabetes for reducing cardiovascular disease events, though their relation to telomerase activity is not well studied. Read More

View Article and Full-Text PDF
September 2020

High homocysteine promotes telomere dysfunction and chromosomal instability in human neuroblastoma SH-SY5Y cells.

Mutat Res 2020 Jun - Jul;854-855:503197. Epub 2020 May 20.

School of Life Sciences, Yunnan Normal University, Kunming, Yunnan, 650500, China; Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education, Kunming, Yunnan, 650500, China. Electronic address:

Telomeres, specialized structures at the ends of linear chromosomes, protect chromosome ends from degradation, recombination, and mis-repair. Critically short telomere length (TL) may result in chromosome instability (CIN), causing tumor promotion and, at higher levels, cell death and tumor suppression. Homocysteine (Hcy) is a sulfur-containing amino acid involved in one-carbon metabolism. Read More

View Article and Full-Text PDF
October 2020

Dataset on the effect of Benzene exposure on genetic damage, hematotoxicity, telomere length and polymorphisms in metabolic and DNA repair genes.

Data Brief 2020 Aug 18;31:105869. Epub 2020 Jun 18.

Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.

In this paper, we present an occupational dataset to evaluate benzene exposure on the effective biomarkers of genetic damage, indicated as cytokinesis-block micronucleus (MN) frequency, hematotoxicity, indicated as white blood cells (WBC) counts, and molecular marker of telomere length (TL). And we further to eliminate the mechanism of benzene induced damage. Then evaluate the effects of sites polymorphism in environmental response genes, including 18 sites in metabolic and DNA repair genes, and the interaction between gene polymorphism and benzene exposure. Read More

View Article and Full-Text PDF

The role of Rif1 in telomere length regulation is separable from its role in origin firing.

Elife 2020 06 29;9. Epub 2020 Jun 29.

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States.

To examine the established link between DNA replication and telomere length, we tested whether firing of telomeric origins would cause telomere lengthening. We found that mutants that block Protein Phosphatase 1 (PP1) binding activated telomeric origins but did not elongate telomeres. In a second approach, we found overexpression of ∆N-Dbf4 and Cdc7 increased DDK activity and activated telomeric origins, yet telomere length was unchanged. Read More

View Article and Full-Text PDF

Telomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish.

Proc Natl Acad Sci U S A 2020 06 17;117(26):15066-15074. Epub 2020 Jun 17.

Telomere and Genome Stability Laboratory, Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal;

Cancer incidence increases exponentially with age when human telomeres are shorter. Similarly, telomerase reverse transcriptase () mutant zebrafish have premature short telomeres and anticipate cancer incidence to younger ages. However, because short telomeres constitute a road block to cell proliferation, telomere shortening is currently viewed as a tumor suppressor mechanism and should protect from cancer. Read More

View Article and Full-Text PDF

Development and optimization of a cascade of screening assays for inhibitors of TRF2.

Anal Biochem 2020 08 30;602:113796. Epub 2020 May 30.

Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China. Electronic address:

TRF2 is a telomere associated protein which plays an important role in telomere maintenance. Knockdown of TRF2 can cause chromosomal end to end fusions and induce DNA damage responses. TRF2 exerts its functions partially by recruiting a number of accessory proteins through its TRF homology domain (TRFH), therefore identification of small molecular compounds which can bind to the TRFH domain of TRF2 and block the interactions of TRF2 with its associated proteins is important to elucidate the molecular mechanism of these protein-protein interactions. Read More

View Article and Full-Text PDF

Interaction effects of environmental response gene polymorphisms and benzene exposure on telomere length in shoe-making workers.

Chemosphere 2020 Sep 7;255:126841. Epub 2020 May 7.

Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. Electronic address:

Benzene is a globally occurring environmental and occupational pollutant that causes leukemia. To better understand telomere length (TL) as a function of benzene toxicity, we recruited 294 shoe-making workers and 102 controls from Wenzhou, China in 2011. Biomarkers of TL, cytokinesis-block micronucleus (MN) frequency, and white blood cells (WBC) were measured. Read More

View Article and Full-Text PDF
September 2020

A new tool for genotoxic risk assessment: Reevaluation of the cytokinesis-block micronucleus assay using semi-automated scoring following telomere and centromere staining.

Mutat Res 2020 Feb - Mar;850-851:503143. Epub 2020 Jan 22.

Cell Environment DNA damage R&D, 75020, Paris, France. Electronic address:

Background: The cytokinesis-block micronucleus (CBMN) assay is an internationally recognized method for measuring DNA damage after exposure to genotoxic agents, as well as a biomarker for DNA repair and chromosomal instability. The high baseline level of micronuclei (MN) in the healthy population has limited the sensitivity and application of the CBMN assay for the follow-up of exposed populations. We reevaluated the sensitivity of the CBNM assay using semi-automated MN scoring following telomere and centromere (TC) staining after in vitro exposure to genotoxic agents (mitomycin or radiation) or aneugenic agents (vinblastine). Read More

View Article and Full-Text PDF

The role of RNA G-quadruplexes in human diseases and therapeutic strategies.

Wiley Interdiscip Rev RNA 2020 01 12;11(1):e1568. Epub 2019 Sep 12.

Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio.

G-quadruplexes (GQs) are four-stranded secondary structures formed by G-rich nucleic acid sequence(s). DNA GQs are present abundantly in the genome and affect a wide range of processes associated with DNA. Recent studies show that RNA GQs are present in different transcripts, including coding and noncoding areas of mRNA, telomeric RNA as well as in other premature and mature noncoding RNAs. Read More

View Article and Full-Text PDF
January 2020

A dynamic link between H/ACA snoRNP components and cytoplasmic stress granules.

Biochim Biophys Acta Mol Cell Res 2019 12 11;1866(12):118529. Epub 2019 Aug 11.

Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126 Napoli, Italy. Electronic address:

Many cell stressors block protein translation, inducing formation of cytoplasmic aggregates. These aggregates, named stress granules (SGs), are composed by translationally stalled ribonucleoproteins and their assembly strongly contributes to cell survival. Composition and dynamics of SGs are thus important starting points for identifying critical factors of the stress response. Read More

View Article and Full-Text PDF
December 2019

Tel1/ATM Signaling to the Checkpoint Contributes to Replicative Senescence in the Absence of Telomerase.

Genetics 2019 10 7;213(2):411-429. Epub 2019 Aug 7.

Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano 20126, Italy

Telomeres progressively shorten at every round of DNA replication in the absence of telomerase. When they become critically short, telomeres trigger replicative senescence by activating a DNA damage response that is governed by the Mec1/ATR and Tel1/ATM protein kinases. While Mec1/ATR is known to block cell division when extended single-stranded DNA (ssDNA) accumulates at eroded telomeres, the molecular mechanism by which Tel1/ATM promotes senescence is still unclear. Read More

View Article and Full-Text PDF
October 2019

A facile deoxyuridine/biotin-modified molecular beacon for simultaneous detection of proteins and nucleic acids via a label-free and background-eliminated fluorescence assay.

Analyst 2019 Sep 7;144(18):5504-5510. Epub 2019 Aug 7.

Department of Biomedical Engineering, Florida International University, 10555 West Flalger Street, Miami, Florida 33174, USA.

Simultaneous detection of different types of cancer biomarkers (nucleic acids and proteins) could facilitate early diagnosis of cancer and clinical treatment. Herein, a simultaneous detection platform of proteins and nucleic acids has been developed using a single substrate probe combining a label-free and background-eliminated fluorescence assay. Telomerase and telomerase RNA (TR) were chosen as the models. Read More

View Article and Full-Text PDF
September 2019

Assessment of the association between ACYP2 and laryngeal squamous cell carcinoma risk in Chinese males.

Mol Genet Genomic Med 2019 07 29;7(7):e00731. Epub 2019 May 29.

Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xi'an, China.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant neoplasms of the upper respiratory tract. Studies have confirmed that an unstable chromosome constitution promotes the progress of laryngeal tumorigenesis, and ACYP2 has been confirmed as a telomere length-related gene. However, to date, the association between ACYP2 polymorphisms and LSCC susceptibility has not been investigated. Read More

View Article and Full-Text PDF

Preferential Binding of π-Ligand Porphyrin Targeting 5'-5' Stacking Interface of Human Telomeric RNA G-Quadruplex Dimer.

J Phys Chem Lett 2019 May 17;10(9):2143-2150. Epub 2019 Apr 17.

College of Chemistry , Beijing Normal University , Beijing 100875 , China.

Human telomeric RNA (TERRA) containing thousands of G-rich repeats has the propensity to form parallel-stranded G-quadruplexes. The emerging crucial roles of TERRA G-quadruplexes in RNA biology fuel increasing attention for studying anticancer ligand binding with such structures, which, however, remains scarce. Here we utilized multiple steady-state and time-resolved spectroscopy analyses in conjunction with NMR methods and investigated thoroughly the binding behavior of TMPyP4 to a TERRA G-quadruplex dimer formed by the 10-nucleotide sequence r(GGGUUAGGGU). Read More

View Article and Full-Text PDF

Mammalian CST averts replication failure by preventing G-quadruplex accumulation.

Nucleic Acids Res 2019 06;47(10):5243-5259

Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China.

Human CST (CTC1-STN1-TEN1) is an RPA-like complex that associates with G-rich single-strand DNA and helps resolve replication problems both at telomeres and genome-wide. We previously showed that CST binds and disrupts G-quadruplex (G4) DNA in vitro, suggesting that CST may prevent in vivo blocks to replication by resolving G4 structures. Here, we demonstrate that CST binds and unfolds G4 with similar efficiency to RPA. Read More

View Article and Full-Text PDF

RNase A treatment and reconstitution with DNA damage response RNA in living cells as a tool to study the role of non-coding RNA in the formation of DNA damage response foci.

Nat Protoc 2019 05 8;14(5):1489-1508. Epub 2019 Apr 8.

IFOM-The FIRC Institute of Molecular Oncology, Milan, Italy.

Non-coding RNA (ncRNA) molecules have been shown to play a variety of cellular roles; however, the contributions of different types of RNA to specific phenomena are often hard to dissect. To study the role of RNA in the assembly of DNA damage response (DDR) foci, we developed the RNase A treatment and reconstitution (RATaR) method, in which cells are mildly permeabilized, incubated with recombinant RNase A and subsequently reconstituted with different RNA species, under conditions of RNase A inactivation and inhibition of endogenous transcription. The block of transcription right after RNase A removal represents a key innovation of RATaR, preventing potential contributions of endogenously neo-synthesized transcripts to the phenotypes studied. Read More

View Article and Full-Text PDF

Physicochemical property based computational scheme for classifying DNA sequence elements of Saccharomyces cerevisiae.

Comput Biol Chem 2019 Apr 26;79:193-201. Epub 2018 Dec 26.

School of Computational and Integrative Sciences, JNU, New Delhi, 110067, India. Electronic address:

GenerationE of huge "omics" data necessitates the development and application of computational methods to annotate the data in terms of biological features. In the context of DNA sequence, it is important to unravel the hidden physicochemical signatures. For this purpose, we have considered various sequence elements such as promoter, ACS, LTRs, telomere, and retrotransposon of the model organism Saccharomyces cerevisiae. Read More

View Article and Full-Text PDF

Adaptation in replicative senescence: a risky business.

Curr Genet 2019 Jun 12;65(3):711-716. Epub 2019 Jan 12.

Sorbonne Université, PSL Research University, CNRS, UMR8226, Institut de Biologie Physico-Chimique, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, 75005, Paris, France.

Cell proliferation is tightly regulated to avoid propagating DNA damage and mutations, which can lead to pathologies such as cancer. To ensure genome integrity, cells activate the DNA damage checkpoint in response to genotoxic lesions to block cell cycle progression. This surveillance mechanism provides time to repair the damage before resuming cell cycle with an intact genome. Read More

View Article and Full-Text PDF

The inhibition of checkpoint activation by telomeres does not involve exclusion of dimethylation of histone H4 lysine 20 (H4K20me2).

F1000Res 2018 9;7:1027. Epub 2018 Jul 9.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.

DNA double-strand breaks (DSBs) activate the DNA damage checkpoint machinery to pause or halt the cell cycle.  Telomeres, the specific DNA-protein complexes at linear eukaryotic chromosome ends, are capped DSBs that do not activate DNA damage checkpoints.  This "checkpoint privileged" status of telomeres was previously investigated in the yeast  lacking the major double-stranded telomere DNA binding protein Taz1. Read More

View Article and Full-Text PDF
September 2019