Готові списки джерел за темами / Telomere Length Protection / Статті в журналах
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Статті в журналах з теми "Telomere Length Protection"

Автор: Grafiati
Опубліковано: 3 червня 2025
Оновлено: 31 липня 2025

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1

Smogorzewska, Agata, Bas van Steensel, Alessandro Bianchi, et al. "Control of Human Telomere Length by TRF1 and TRF2." Molecular and Cellular Biology 20, no. 5 (2000): 1659–68. http://dx.doi.org/10.1128/mcb.20.5.1659-1668.2000.

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Анотація:
ABSTRACT Telomere length in human cells is controlled by a homeostasis mechanism that involves telomerase and the negative regulator of telomere length, TRF1 (TTAGGG repeat binding factor 1). Here we report that TRF2, a TRF1-related protein previously implicated in protection of chromosome ends, is a second negative regulator of telomere length. Overexpression of TRF2 results in the progressive shortening of telomere length, similar to the phenotype observed with TRF1. However, while induction of TRF1 could be maintained over more than 300 population doublings and resulted in stable, short tel
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2

Mattern, Karin A., Susan J. J. Swiggers, Alex L. Nigg, Bob Löwenberg, Adriaan B. Houtsmuller, and J. Mark J. M. Zijlmans. "Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function." Molecular and Cellular Biology 24, no. 12 (2004): 5587–94. http://dx.doi.org/10.1128/mcb.24.12.5587-5594.2004.

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Анотація:
ABSTRACT Telomeric proteins have an essential role in the regulation of the length of the telomeric DNA tract and in protection against end-to-end chromosome fusion. Telomere organization and how individual proteins are involved in different telomere functions in living cells is largely unknown. By using green fluorescent protein tagging and photobleaching, we investigated in vivo interactions of human telomeric DNA-binding proteins with telomeric DNA. Our results show that telomeric proteins interact with telomeres in a complex dynamic fashion: TRF2, which has a dual role in chromosome end pr
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3

Bunch, Jeremy T., Nancy S. Bae, Jessica Leonardi, and Peter Baumann. "Distinct Requirements for Pot1 in Limiting Telomere Length and Maintaining Chromosome Stability." Molecular and Cellular Biology 25, no. 13 (2005): 5567–78. http://dx.doi.org/10.1128/mcb.25.13.5567-5578.2005.

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ABSTRACT The fission yeast Pot1 (protection of telomeres) protein binds to the single-stranded extensions at the ends of telomeres, where its presence is critical for the maintenance of linear chromosomes. Homologs of Pot1 have been identified in a wide variety of eukaryotes, including plants, animals, and humans. We now show that Pot1 plays dual roles in telomere length regulation and chromosome end protection. Using a series of Pot1 truncation mutants, we have defined distinct areas of the protein required for chromosome stability and for limiting access to telomere ends by telomerase. We pr
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4

Donate, Luis E., and Maria A. Blasco. "Telomeres in cancer and ageing." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1561 (2011): 76–84. http://dx.doi.org/10.1098/rstb.2010.0291.

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Анотація:
Telomeres protect the chromosome ends from unscheduled DNA repair and degradation. Telomeres are heterochromatic domains composed of repetitive DNA (TTAGGG repeats) bound to an array of specialized proteins. The length of telomere repeats and the integrity of telomere-binding proteins are both important for telomere protection. Furthermore, telomere length and integrity are regulated by a number of epigenetic modifications, thus pointing to higher order control of telomere function. In this regard, we have recently discovered that telomeres are transcribed generating long, non-coding RNAs, whi
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5

Hsu, Joseph K., Tao Lin, and Robert Y. L. Tsai. "Nucleostemin prevents telomere damage by promoting PML-IV recruitment to SUMOylated TRF1." Journal of Cell Biology 197, no. 5 (2012): 613–24. http://dx.doi.org/10.1083/jcb.201109038.

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Анотація:
Continuously dividing cells must be protected from telomeric and nontelomeric DNA damage in order to maintain their proliferative potential. Here, we report a novel telomere-protecting mechanism regulated by nucleostemin (NS). NS depletion increased the number of telomere damage foci in both telomerase-active (TA+) and alternative lengthening of telomere (ALT) cells and decreased the percentage of damaged telomeres associated with ALT-associated PML bodies (APB) and the number of APB in ALT cells. Mechanistically, NS could promote the recruitment of PML-IV to SUMOylated TRF1 in TA+ and ALT cel
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6

Fernandes, Stina George, Rebecca Dsouza, Gouri Pandya, et al. "Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential." Cancers 12, no. 7 (2020): 1901. http://dx.doi.org/10.3390/cancers12071901.

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Анотація:
Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects t
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7

Kelleher, Colleen, Isabel Kurth, and Joachim Lingner. "Human Protection of Telomeres 1 (POT1) Is a Negative Regulator of Telomerase Activity In Vitro." Molecular and Cellular Biology 25, no. 2 (2005): 808–18. http://dx.doi.org/10.1128/mcb.25.2.808-818.2005.

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Анотація:
ABSTRACT The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects telomeres from rapid degradation in Schizosaccharomyces pombe and has been implicated in positive and negative telomere length regulation in humans. Human POT1 appears to interact with telomeres both through direct binding to the 3′ overhanging G-strand DNA and through interaction with the TRF1 duplex telomere DNA binding complex. The influence of POT1 on telomerase activity has not been studied at the molecular level. We show here that POT1 negatively effects telomerase activity in vitro. We fin
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8

Caslini, Corrado, and Amparo Serna. "Telomere Transcription in MLL-Rearranged Leukemia Cell Lines: Increased Levels of TERRA Associate with Lymphoid Lineage and Are Independent of Telomere Length and Ploidy." Biomedicines 11, no. 3 (2023): 925. http://dx.doi.org/10.3390/biomedicines11030925.

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Анотація:
Telomere transcription into telomeric repeat-containing RNA (TERRA) is an integral component of all aspects of chromosome end protection consisting of telomerase- or recombination-dependent telomere elongation, telomere capping, and the preservation of the (sub)telomeric heterochromatin structure. The chromatin modifier and transcriptional regulator MLL binds to telomeres and regulates TERRA transcription in telomere length homeostasis and response to telomere dysfunction. MLL fusion proteins (MLL-FPs), the product of MLL rearrangements in leukemia, also bind to telomeric chromatin. However, a
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9

Fan, Hueng-Chuen, Fung-Wei Chang, Jeng-Dau Tsai, et al. "Telomeres and Cancer." Life 11, no. 12 (2021): 1405. http://dx.doi.org/10.3390/life11121405.

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Анотація:
Telomeres cap the ends of eukaryotic chromosomes and are indispensable chromatin structures for genome protection and replication. Telomere length maintenance has been attributed to several functional modulators, including telomerase, the shelterin complex, and the CST complex, synergizing with DNA replication, repair, and the RNA metabolism pathway components. As dysfunctional telomere maintenance and telomerase activation are associated with several human diseases, including cancer, the molecular mechanisms behind telomere length regulation and protection need particular emphasis. Cancer cel
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10

Kalmykova, Alla. "Telomere Checkpoint in Development and Aging." International Journal of Molecular Sciences 24, no. 21 (2023): 15979. http://dx.doi.org/10.3390/ijms242115979.

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Анотація:
The maintenance of genome integrity through generations is largely determined by the stability of telomeres. Increasing evidence suggests that telomere dysfunction may trigger changes in cell fate, independently of telomere length. Telomeric multiple tandem repeats are potentially highly recombinogenic. Heterochromatin formation, transcriptional repression, the suppression of homologous recombination and chromosome end protection are all required for telomere stability. Genetic and epigenetic defects affecting telomere homeostasis may cause length-independent internal telomeric DNA damage. Gro
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11

Shakirov, Eugene V., Yulia V. Surovtseva, Nathan Osbun, and Dorothy E. Shippen. "The Arabidopsis Pot1 and Pot2 Proteins Function in Telomere Length Homeostasis and Chromosome End Protection." Molecular and Cellular Biology 25, no. 17 (2005): 7725–33. http://dx.doi.org/10.1128/mcb.25.17.7725-7733.2005.

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Анотація:
ABSTRACT Pot1 (protection of telomeres 1) is a single-stranded telomere binding protein that is essential for chromosome end protection and telomere length homeostasis. Arabidopsis encodes two Pot1-like proteins, dubbed AtPot1 and AtPot2. Here we show that telomeres in transgenic plants expressing a truncated AtPot1 allele lacking the N-terminal oligonucleotide/oligosaccharide binding fold (P1ΔN) are 1 to 1.5 kb shorter than in the wild type, suggesting that AtPot1 contributes to the positive regulation of telomere length control. In contrast, telomere length is unperturbed in plants expressin
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12

Swiggers, Susan J. J., Marianne A. Kuijpers, Maartje J. de Cort, Berna Beverloo, and J. Mark J. M. Zijlmans. "Extensive Chromosome Instability in Acute Myeloid Leukemia Is Associated with Critical Telomere Shortening." Blood 104, no. 11 (2004): 3376. http://dx.doi.org/10.1182/blood.v104.11.3376.3376.

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Анотація:
Abstract Telomeres, the ends of linear chromosomes, have a critical role in protection against chromosome end-to-end fusion. Telomeres shorten in every cell division due to the end replication problem. Telomerase is a reverse transcriptase that adds telomeric DNA repeats to the ultimate chromosome end. In vitro models of long-term fibroblast cultures have identified two sequential mortality stages, senescence (M1) and crisis (M2). Senescence can be bypassed by loss of p53 or Rb function, whereas escape from crisis can only be achieved by activating a telomere maintenance mechanism, mostly telo
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13

Srinivas, Nalini, Sivaramakrishna Rachakonda, and Rajiv Kumar. "Telomeres and Telomere Length: A General Overview." Cancers 12, no. 3 (2020): 558. http://dx.doi.org/10.3390/cancers12030558.

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Анотація:
Telomeres are highly conserved tandem nucleotide repeats that include proximal double-stranded and distal single-stranded regions that in complex with shelterin proteins afford protection at chromosomal ends to maintain genomic integrity. Due to the inherent limitations of DNA replication and telomerase suppression in most somatic cells, telomeres undergo age-dependent incremental attrition. Short or dysfunctional telomeres are recognized as DNA double-stranded breaks, triggering cells to undergo replicative senescence. Telomere shortening, therefore, acts as a counting mechanism that drives r
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14

DuBois, Michelle L., Zara W. Haimberger, Martin W. McIntosh, and Daniel E. Gottschling. "A Quantitative Assay for Telomere Protection in Saccharomyces cerevisiae." Genetics 161, no. 3 (2002): 995–1013. http://dx.doi.org/10.1093/genetics/161.3.995.

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Анотація:
Abstract Telomeres are the protective ends of linear chromosomes. Telomeric components have been identified and described by their abilities to bind telomeric DNA, affect telomere repeat length, participate in telomeric DNA replication, or modulate transcriptional silencing of telomere-adjacent genes; however, their roles in chromosome end protection are not as well defined. We have developed a genetic, quantitative assay in Saccharomyces cerevisiae to measure whether various telomeric components protect chromosome ends from homologous recombination. This “chromosomal cap” assay has revealed t
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15

Ray, Alo, and Kurt W. Runge. "The C Terminus of the Major Yeast Telomere Binding Protein Rap1p Enhances Telomere Formation." Molecular and Cellular Biology 18, no. 3 (1998): 1284–95. http://dx.doi.org/10.1128/mcb.18.3.1284.

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Анотація:
ABSTRACT The telomeres of most organisms consist of short repeated sequences that can be elongated by telomerase, a reverse transcriptase complex that contains its own RNA template for the synthesis of telomere repeats. In Saccharomyces cerevisiae, the RAP1gene encodes the major telomere binding protein Rap1p. Here we use a quantitative telomere formation assay to demonstrate that Rap1p C termini can enhance telomere formation more than 30-fold when they are located at internal sites. This stimulation is distinct from protection from degradation. Enhancement of formation required the gene for
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16

Linger, Benjamin R., Gregg B. Morin, and Carolyn M. Price. "The Pot1a-associated proteins Tpt1 and Pat1 coordinate telomere protection and length regulation in Tetrahymena." Molecular Biology of the Cell 22, no. 21 (2011): 4161–70. http://dx.doi.org/10.1091/mbc.e11-06-0551.

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Анотація:
We have identified two new telomere proteins, Tpt1 and Pat1, from the ciliate Tetrahymena thermophila. Although Tetrahymena telomerase is well characterized, only one telomere protein had previously been identified. This was the G-overhang binding-protein Pot1a. Tpt1 and Pat1 were isolated as Pot1a binding partners and shown to localize to telomeres. As Tpt1 and Pat1 were both found to be essential, conditional cell lines were generated to explore their function. Tpt1 depletion caused a rapid growth arrest and telomere elongation in the absence of cell division. The phenotype was similar to th
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17

Palacios, Jose A., Daniel Herranz, Maria Luigia De Bonis, Susana Velasco, Manuel Serrano, and Maria A. Blasco. "SIRT1 contributes to telomere maintenance and augments global homologous recombination." Journal of Cell Biology 191, no. 7 (2010): 1299–313. http://dx.doi.org/10.1083/jcb.201005160.

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Анотація:
Yeast Sir2 deacetylase is a component of the silent information regulator (SIR) complex encompassing Sir2/Sir3/Sir4. Sir2 is recruited to telomeres through Rap1, and this complex spreads into subtelomeric DNA via histone deacetylation. However, potential functions at telomeres for SIRT1, the mammalian orthologue of yeast Sir2, are less clear. We studied both loss of function (SIRT1 deficient) and gain of function (SIRT1super) mouse models. Our results indicate that SIRT1 is a positive regulator of telomere length in vivo and attenuates telomere shortening associated with aging, an effect depen
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18

Adwan Shekhidem, Huda, Lital Sharvit, Derek M. Huffman, Irena Manov, Gil Atzmon, and Imad Shams. "Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity." Genes 14, no. 4 (2023): 845. http://dx.doi.org/10.3390/genes14040845.

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Анотація:
Telomere shortening or loss of shelterin components activates DNA damage response (DDR) pathways, leading to a replicative senescence that is usually coupled with a senescence-associated secretory phenotype (SASP). Recent studies suggested that telomere aberration that activates DDR may occur, irrespective of telomere length or loss of shelterin complex. The blind mole-rat (Spalax) is a subterranean rodent with exceptional longevity, and its cells demonstrate an uncoupling of senescence and SASP inflammatory components. Herein, we evaluated Spalax relative telomere length, telomerase activity,
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19

Alt, Christina, Menelaos Tsapekos, Diego Perez, Joachim Klode, and Ingo Stoffels. "An Open-Label Clinical Trial Analyzing the Efficacy of a Novel Telomere-Protecting Antiaging Face Cream." Cosmetics 9, no. 5 (2022): 95. http://dx.doi.org/10.3390/cosmetics9050095.

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Анотація:
Telomere length, a hallmark of cellular senescence, decreases with age and is associated with age-related diseases. Environmental factors, including dietary and lifestyle factors, can affect the rate at which telomeres shorten, and telomere protection prevents this from happening. The protection of telomeres by natural molecules has been proposed as an antiaging strategy that may play a role in treating age-related diseases. This study investigated the effect of a cycloartane-type triterpene glycoside (astragaloside IV). Astragaloside IV is one of the primary compounds from the aqueous extract
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20

Xu, Ling, Ruben C. Petreaca, Hovik J. Gasparyan, Stephanie Vu, and Constance I. Nugent. "TEN1 Is Essential for CDC13-Mediated Telomere Capping." Genetics 183, no. 3 (2009): 793–810. http://dx.doi.org/10.1534/genetics.109.108894.

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Анотація:
Telomere binding proteins protect chromosome ends from degradation and mask chromosome termini from checkpoint surveillance. In Saccharomyces cerevisiae, Cdc13 binds single-stranded G-rich telomere repeats, maintaining telomere integrity and length. Two additional proteins, Ten1 and Stn1, interact with Cdc13 but their contributions to telomere integrity are not well defined. Ten1 is known to prevent accumulation of aberrant single-stranded telomere DNA; whether this results from defective end protection or defective telomere replication is unclear. Here we report our analysis of a new group of
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21

Longhese, Maria Pia, Vera Paciotti, Holger Neecke, and Giovanna Lucchini. "Checkpoint Proteins Influence Telomeric Silencing and Length Maintenance in Budding Yeast." Genetics 155, no. 4 (2000): 1577–91. http://dx.doi.org/10.1093/genetics/155.4.1577.

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AbstractA complex network of surveillance mechanisms, called checkpoints, interrupts cell cycle progression when damage to the genome is detected or when cells fail to complete DNA replication, thus ensuring genetic integrity. In budding yeast, components of the DNA damage checkpoint regulatory network include the RAD9, RAD17, RAD24, MEC3, DDC1, RAD53, and MEC1 genes that are proposed to be involved in different aspects of DNA metabolism. We provide evidence that some DNA damage checkpoint components play a role in maintaining telomere integrity. In fact, rad53 mutants specifically enhance rep
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22

Calado, Rodrigo T. "Telomeres and marrow failure." Hematology 2009, no. 1 (2009): 338–43. http://dx.doi.org/10.1182/asheducation-2009.1.338.

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Анотація:
AbstractTelomeres, repeat sequences at the ends of chromosomes, are protective chromosomal structures highly conserved from primitive organisms to humans. Telomeres inevitably shorten with every cell cycle, and telomere attrition has been hypothesized to be fundamental to normal senescence of cells, tissues, and organisms. Molecular mechanisms have evolved to maintain their length and protective function; telomerase (TERT) is a reverse transcriptase enzyme that uses an RNA molecule (TERC) as the template to elongate the 3′ ends of telomeres. Shelterin is a collection of DNA-binding proteins th
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23

Harrington, Lea, and Fabio Pucci. "In medio stat virtus : unanticipated consequences of telomere dysequilibrium." Philosophical Transactions of the Royal Society B: Biological Sciences 373, no. 1741 (2018): 20160444. http://dx.doi.org/10.1098/rstb.2016.0444.

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Анотація:
The integrity of chromosome ends, or telomeres, depends on myriad processes that must balance the need to compact and protect the telomeric, G-rich DNA from detection as a double-stranded DNA break, and yet still permit access to enzymes that process, replicate and maintain a sufficient reserve of telomeric DNA. When unable to maintain this equilibrium, erosion of telomeres leads to perturbations at or near the telomeres themselves, including loss of binding by the telomere protective complex, shelterin, and alterations in transcription and post-translational modifications of histones. Althoug
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24

Wu, Yangxiu, Rebecca C. Poulos, and Roger R. Reddel. "Role of POT1 in Human Cancer." Cancers 12, no. 10 (2020): 2739. http://dx.doi.org/10.3390/cancers12102739.

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Анотація:
Telomere abnormalities facilitate cancer development by contributing to genomic instability and cellular immortalization. The Protection of Telomeres 1 (POT1) protein is an essential subunit of the shelterin telomere binding complex. It directly binds to single-stranded telomeric DNA, protecting chromosomal ends from an inappropriate DNA damage response, and plays a role in telomere length regulation. Alterations of POT1 have been detected in a range of cancers. Here, we review the biological functions of POT1, the prevalence of POT1 germline and somatic mutations across cancer predisposition
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25

de la Guardia, Rafael Díaz, Carolina Elosua, Purificación Catalina, et al. "Expression Profile and up-Regulation of Telomere-Associated Proteins In Multiple Myeloma." Blood 116, no. 21 (2010): 4050. http://dx.doi.org/10.1182/blood.v116.21.4050.4050.

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Abstract Abstract 4050 The role of the telomeres in the mechanisms of ageing and carcinogenesis has generated a considerable interest as a novel approach to the treatment of many cancers. Telomeres are nucleoproteins structures that protect the ends of eukaryotic chromosomes, which are particularly vulnerable due to progressive shortening in almost all dividing cells. The telomere length was observed as a critical factor in the initiation and progression of human cancers, and it is associated to chromosomal instability. Most immortal cells possess enzymatic activity of telomerase. This suggest
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26

Baliou, Stella, Petros Ioannou, Miruna-Maria Apetroaei, et al. "The Impact of the Mediterranean Diet on Telomere Biology: Implications for Disease Management—A Narrative Review." Nutrients 16, no. 15 (2024): 2525. http://dx.doi.org/10.3390/nu16152525.

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Анотація:
Introduction: Telomeres are nucleoprotein complexes at the ends of chromosomes that are under the control of genetic and environmental triggers. Accelerated telomere shortening is causally implicated in the increasing incidence of diseases. The Mediterranean diet has recently been identified as one that confers protection against diseases. This review aimed to identify the effect of each component of the Mediterranean diet on telomere length dynamics, highlighting the underlying molecular mechanisms. Methods: PubMed was searched to identify relevant studies to extract data for conducting a nar
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27

Hofr, Ctirad, Pavla Šultesová, Michal Zimmermann, et al. "Single-Myb-histone proteins from Arabidopsis thaliana: a quantitative study of telomere-binding specificity and kinetics." Biochemical Journal 419, no. 1 (2009): 221–30. http://dx.doi.org/10.1042/bj20082195.

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Анотація:
Proteins that bind telomeric DNA modulate the structure of chromosome ends and control telomere function and maintenance. It has been shown that AtTRB (Arabidopsis thaliana telomere-repeat-binding factor) proteins from the SMH (single-Myb-histone) family selectively bind double-stranded telomeric DNA and interact with the telomeric protein AtPOT1b (A. thaliana protection of telomeres 1b), which is involved in telomere capping. In the present study, we performed the first quantitative DNA-binding study of this plant-specific family of proteins. Interactions of full-length proteins AtTRB1 and At
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28

Sánchez-Vázquez, Raúl, Paula Martínez, and Maria A. Blasco. "AKT-dependent signaling of extracellular cues through telomeres impact on tumorigenesis." PLOS Genetics 17, no. 3 (2021): e1009410. http://dx.doi.org/10.1371/journal.pgen.1009410.

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Анотація:
The telomere-bound shelterin complex is essential for chromosome-end protection and genomic stability. Little is known on the regulation of shelterin components by extracellular signals including developmental and environmental cues. Here, we show that human TRF1 is subjected to AKT-dependent regulation. To study the importance of this modification in vivo, we generate knock-in human cell lines carrying non-phosphorylatable mutants of the AKT-dependent TRF1 phosphorylation sites by CRISPR-Cas9. We find that TRF1 mutant cells show decreased TRF1 binding to telomeres and increased global and tel
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29

Dudinskaya, Ekaterina N., Olga N. Tkacheva, Natalia V. Brailova, Irina D. Strazhesko, and Marina V. Shestakova. "Telomere biology and metabolic disorders: the role of insulin resistance and type 2 diabetes." Problems of Endocrinology 66, no. 4 (2020): 35–44. http://dx.doi.org/10.14341/probl12510.

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BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different “genetic protection” of cells, which many scientists associate with replicative cellular aging.AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin.MATERIALS AND METHODS: The observation study included 305 patients. The parameters of
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30

Stoklosa, Tomasz, Anna Deregowska, Katarzyna Pruszczyk, et al. "Role of Shelterin Complex and Alternative Telomere Lengthening in Genomic Instability and Disease Progression in Chronic Myeloid Leukemia." Blood 128, no. 22 (2016): 1880. http://dx.doi.org/10.1182/blood.v128.22.1880.1880.

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Анотація:
Abstract Genomic instability has many sources, among others, shortening of telomeres, nucleoprotein complexes located at the ends of chromosomes. Tumor cells have aberrant mechanisms of telomere maintenance: their telomeres are shortened, no longer preventing chromosome end-to-end fusion and recombination, but frequently not short enough to lead to cell senescence. Both telomerase and shelterin complexes are involved in telomere homeostasis. Reduction in the telomere length is considered as one of the features of chronic myeloid leukemia (CML) similar to other human malignancies and telomere s
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31

Churikov, Dmitri, Chao Wei, and Carolyn M. Price. "Vertebrate POT1 Restricts G-Overhang Length and Prevents Activation of a Telomeric DNA Damage Checkpoint but Is Dispensable for Overhang Protection." Molecular and Cellular Biology 26, no. 18 (2006): 6971–82. http://dx.doi.org/10.1128/mcb.01011-06.

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Анотація:
ABSTRACT Although vertebrate POT1 is thought to play a role in both telomere capping and length regulation, its function has proved difficult to analyze. We therefore generated a conditional cell line that lacks wild-type POT1 but expresses an estrogen receptor-POT1 fusion. The cells grow normally in tamoxifen, but drug removal causes loss of POT1 from the telomere, rapid cell cycle arrest, and eventual cell death. The arrested cells have a 4N DNA content, and addition of caffeine causes immediate entry into mitosis, suggesting a G2 arrest due to an ATM- and/or ATR-mediated checkpoint. γH2AX a
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32

Mustafa, Golam, Sajad Shiekh, Keshav GC, Sanjaya Abeysirigunawardena, and Hamza Balci. "Interrogating accessibility of telomeric sequences with FRET-PAINT: evidence for length-dependent telomere compaction." Nucleic Acids Research 49, no. 6 (2021): 3371–80. http://dx.doi.org/10.1093/nar/gkab067.

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Abstract 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
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33

Ueno, Masaru. "Exploring Genetic Interactions with Telomere Protection Gene pot1 in Fission Yeast." Biomolecules 13, no. 2 (2023): 370. http://dx.doi.org/10.3390/biom13020370.

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Анотація:
The regulation of telomere length has a significant impact on cancer risk and aging in humans. Circular chromosomes are found in humans and are often unstable during mitosis, resulting in genome instability. Some types of cancer have a high frequency of a circular chromosome. Fission yeast is a good model for studying the formation and stability of circular chromosomes as deletion of pot1 (encoding a telomere protection protein) results in rapid telomere degradation and chromosome fusion. Pot1 binds to single-stranded telomere DNA and is conserved from fission yeast to humans. Loss of pot1 lea
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34

Kulak, Ozlem, Hua Chen, Brody Holohan та ін. "Disruption of Wnt/β-Catenin Signaling and Telomeric Shortening Are Inextricable Consequences of Tankyrase Inhibition in Human Cells". Molecular and Cellular Biology 35, № 14 (2015): 2425–35. http://dx.doi.org/10.1128/mcb.00392-15.

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Анотація:
Maintenance of chromosomal ends (telomeres) directly contributes to cancer cell immortalization. The telomere protection enzymes belonging to the tankyrase (Tnks) subfamily of poly(ADP-ribose) polymerases (PARPs) have recently been shown to also control transcriptional response to secreted Wnt signaling molecules. Whereas Tnks inhibitors are currently being developed as therapeutic agents for targeting Wnt-related cancers and as modulators of Wnt signaling in tissue-engineering agendas, their impact on telomere length maintenance remains unclear. Here, we leveraged a collection of Wnt pathway
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35

Dantzer, Françoise, Marie-Josèphe Giraud-Panis, Isabel Jaco, et al. "Functional Interaction between Poly(ADP-Ribose) Polymerase 2 (PARP-2) and TRF2: PARP Activity Negatively Regulates TRF2." Molecular and Cellular Biology 24, no. 4 (2004): 1595–607. http://dx.doi.org/10.1128/mcb.24.4.1595-1607.2004.

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ABSTRACT The DNA damage-dependent poly(ADP-ribose) polymerase-2 (PARP-2) is, together with PARP-1, an active player of the base excision repair process, thus defining its key role in genome surveillance and protection. Telomeres are specialized DNA-protein structures that protect chromosome ends from being recognized and processed as DNA strand breaks. In mammals, telomere protection depends on the T2AG3 repeat binding protein TRF2, which has been shown to remodel telomeres into large duplex loops (t-loops). In this work we show that PARP-2 physically binds to TRF2 with high affinity. The asso
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36

Shan, Jiaheng, Jianxia Mo, Chenyue An, Lan Xiang та Jianhua Qi. "β-Cyclocitral from Lavandula angustifolia Mill. Exerts Anti-Aging Effects on Yeasts and Mammalian Cells via Telomere Protection, Antioxidative Stress, and Autophagy Activation". Antioxidants 13, № 6 (2024): 715. http://dx.doi.org/10.3390/antiox13060715.

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We used a replicative lifespan (RLS) experiment of K6001 yeast to screen for anti-aging compounds within lavender extract (Lavandula angustifolia Mill.), leading to the discovery of β-cyclocitral (CYC) as a potential anti-aging compound. Concurrently, the chronological lifespan (CLS) of YOM36 yeast and mammalian cells confirmed the anti-aging effect of CYC. This molecule extended the yeast lifespan and inhibited etoposide (ETO)-induced cell senescence. To understand the mechanism of CYC, we analyzed its effects on telomeres, oxidative stress, and autophagy. CYC administration resulted in notab
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37

Fice, Heather, and Bernard Robaire. "Telomere Dynamics Throughout Spermatogenesis." Genes 10, no. 7 (2019): 525. http://dx.doi.org/10.3390/genes10070525.

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Анотація:
Telomeres are repeat regions of DNA that cap either end of each chromosome, thereby providing stability and protection from the degradation of gene-rich regions. Each cell replication causes the loss of telomeric repeats due to incomplete DNA replication, though it is well-established that progressive telomere shortening is evaded in male germ cells by the maintenance of active telomerase. However, germ cell telomeres are still susceptible to disruption or insult by oxidative stress, toxicant exposure, and aging. Our aim was to examine the relative telomere length (rTL) in an outbred Sprague D
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38

de Carvalho Cunha, Verusca, Thiago dos Santos Rosa, Marcelo Sales, et al. "Training Performed Above Lactate Threshold Decreases p53 and Shelterin Expression in Mice." International Journal of Sports Medicine 39, no. 09 (2018): 704–11. http://dx.doi.org/10.1055/a-0631-3441.

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AbstractTelomere shortening is associated to sarcopenia leading to functional impairment during aging. There are mechanisms associated with telomere attrition, as well to its protection and repair. Physical training is a factor that attenuates telomere shortening, but little is known about the effects of different exercise intensities on telomere biology. Thus, we evaluated the effects of exercise intensity (moderate vs. high-intensity domain) on gene expression of senescence markers Checkpoint kinase 2 and tumor suppressor (Chk2 and p53, respectively), shelterin telomere repeat binding 1 and
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39

Rubtsova, Maria, and Olga Dontsova. "Human Telomerase RNA: Telomerase Component or More?" Biomolecules 10, no. 6 (2020): 873. http://dx.doi.org/10.3390/biom10060873.

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Анотація:
Telomerase is a ribonucleoprotein complex that maintains the lengths of telomeres. Most studies of telomerase function have focused on the involvement of telomerase activation in the immortalization of cancer cells and cellular rejuvenation. However, some studies demonstrated that the results do not meet expectations for telomerase action in telomere maintenance. Recent results give reason to think that major telomerase components—the reverse transcriptase protein subunit and telomerase RNA—may participate in many cellular processes, including the regulation of apoptosis and autophagy, cell su
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40

Yu, Eun Young, Wei-Feng Yen, Olga Steinberg-Neifach, and Neal F. Lue. "Rap1 in Candida albicans: an Unusual Structural Organization and a Critical Function in Suppressing Telomere Recombination." Molecular and Cellular Biology 30, no. 5 (2009): 1254–68. http://dx.doi.org/10.1128/mcb.00986-09.

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ABSTRACT Rap1 (repressor activator protein 1) is a conserved multifunctional protein initially identified as a transcriptional regulator of ribosomal protein genes in Saccharomyces cerevisiae but subsequently shown to play diverse functions at multiple chromosomal loci, including telomeres. The function of Rap1 appears to be evolutionarily plastic, especially in the budding yeast lineages. We report here our biochemical and molecular genetic characterizations of Candida albicans Rap1, which exhibits an unusual, miniaturized domain organization in comparison to the S. cerevisiae homologue. We s
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41

Abdulkina, Liliia R., Inna A. Agabekian, Liia R. Valeeva, Olga S. Kozlova, Margarita R. Sharipova, and Eugene V. Shakirov. "Comparative Application of Terminal Restriction Fragment Analysis Tools to Large-Scale Genomic Assays." International Journal of Molecular Sciences 24, no. 24 (2023): 17194. http://dx.doi.org/10.3390/ijms242417194.

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Анотація:
The analysis of telomere length is an important component of many studies aiming to characterize the role of telomere maintenance mechanisms in cellular lifespan, disease, or in general chromosome protection and DNA replication pathways. Several powerful methods to accurately measure the telomere length from Southern blots have been developed, but their utility for large-scale genomic studies has not been previously evaluated. Here, we performed a comparative analysis of two recently developed programs, TeloTool and WALTER, for the extraction of mean telomere length values from Southern blots.
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42

Chen, Liuh-Yow, Dan Liu, and Zhou Songyang. "Telomere Maintenance through Spatial Control of Telomeric Proteins." Molecular and Cellular Biology 27, no. 16 (2007): 5898–909. http://dx.doi.org/10.1128/mcb.00603-07.

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Анотація:
ABSTRACT The six human telomeric proteins TRF1, TRF2, RAP1, TIN2, POT1, and TPP1 can form a complex called the telosome/shelterin, which is required for telomere protection and length control. TPP1 has been shown to regulate both POT1 telomere localization and telosome assembly through its binding to TIN2. It remains to be determined where such interactions take place and whether cellular compartmentalization of telomeric proteins is important for telomere maintenance. We systematically investigated here the cellular localization and interactions of human telomeric proteins. Interestingly, we
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43

Harada, Kunyu, Kaoru Kurisu, Hidetoshi Tahara, Eiji Tahara, Toshinori Ide, and Eiichi Tahara. "Telomerase activity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker." Journal of Neurosurgery 93, no. 4 (2000): 618–25. http://dx.doi.org/10.3171/jns.2000.93.4.0618.

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Object. Telomerase activity is responsible for cell immortality. To examine the role of telomerase in the carcinogenesis of human glioblastomas multiforme (GBMs), the authors studied telomerase activity, telomerase component expression, and telomere lengths in 42 GBM samples.Methods. In all samples, EGFR and MDM2 amplifications and overexpressions were examined using Southern and Northern blot analyses. The p53 mutation was analyzed using polymerase chain reaction—single strand conformational polymorphism and by direct sequence analysis. Specimens of tissues were immunostained with p53, EGFR,
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44

He, Hua, Yang Wang, Xiaolan Guo, et al. "Pot1b Deletion and Telomerase Haploinsufficiency in Mice Initiate an ATR-Dependent DNA Damage Response and Elicit Phenotypes Resembling Dyskeratosis Congenita." Molecular and Cellular Biology 29, no. 1 (2008): 229–40. http://dx.doi.org/10.1128/mcb.01400-08.

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Анотація:
ABSTRACT The Protection of telomeres 1 (POT1) protein is a single-stranded telomere binding protein that is essential for proper maintenance of telomere length. Disruption of POT1 function leads to chromosome instability and loss of cellular viability. Here, we show that targeted deletion of the mouse Pot1b gene results in increased apoptosis in highly proliferative tissues. In the setting of telomerase haploinsufficiency, loss of Pot1b results in depletion of germ cells and complete bone marrow failure due to increased apoptosis, culminating in premature death. Pot1b −/ − mTR +/ − hematopoiet
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45

Savage, Sharon A., Neelam Giri, Gabriela M. Baerlocher, Nick Orr, Peter M. Lansdorp, and Blanche P. Alter. "TINF2, a Component of the Shelterin Telomere Protection Complex, Is Mutated in Dyskeratosis Congenita." Blood 110, no. 11 (2007): 835. http://dx.doi.org/10.1182/blood.v110.11.835.835.

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Abstract Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the triad of abnormal nails, lacey reticular skin pigmentation, and oral leukoplakia. Patients with DC are at high risk of developing aplastic anemia, myelodysplastic syndrome and leukemia. Diagnosis of DC is challenging due to variability of the triad and heterogeneous clinical findings such as pulmonary and liver disease, avascular necrosis, esophageal or urethral stenosis and development delay. The unifying feature in DC is exceedingly short telomere lengths and defects in telomere biology. Ge
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46

Zhang, Yanbo, Yi Guo, Gouqing Zhou, and Shuang Li. "Regulation of Telomere Length and Atherosclerosis by Protection of Telomeres 1 Protein." Journal of Nanoscience and Nanotechnology 19, no. 12 (2019): 7953–59. http://dx.doi.org/10.1166/jnn.2019.16938.

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47

Springhetti, Sina, Vesna Bucan, Christina Liebsch, Andrea Lazaridis, Peter Maria Vogt, and Sarah Strauß. "An Identification and Characterization of the Axolotl (Ambystoma mexicanum, Amex) Telomerase Reverse Transcriptase (Amex TERT)." Genes 13, no. 2 (2022): 373. http://dx.doi.org/10.3390/genes13020373.

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The Mexican axolotl is one of the few vertebrates that is able to replace its lost body parts during lifespan. Due to its remarkable regenerative abilities, the axolotl emerged as a model organism especially for limb regeneration. Telomeres and the telomerase enzyme are crucial for regeneration and protection against aging processes and degenerating diseases. Despite its relevance for regeneration, the axolotl telomerase and telomere length have not yet been investigated. Therefore, in the present paper, we reveal the sequence of the axolotl telomerase reverse transcriptase gene (Tert) and pro
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48

Jacob, Naduparambil K., Rachel Lescasse, Benjamin R. Linger, and Carolyn M. Price. "Tetrahymena POT1a Regulates Telomere Length and Prevents Activation of a Cell CycleCheckpoint." Molecular and Cellular Biology 27, no. 5 (2006): 1592–601. http://dx.doi.org/10.1128/mcb.01975-06.

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ABSTRACT The POT1/TEBP telomere proteins are a group of single-stranded DNA (ssDNA)-binding proteins that have long been assumed to protect the G overhang on the telomeric 3′ strand. We have found that the Tetrahymena thermophila genome contains two POT1 gene homologs, POT1a and POT1b. The POT1a gene is essential, but POT1b is not. We have generated a conditional POT1a cell line and shown that POT1a depletion results in a monster cell phenotype and growth arrest. However, G-overhang structure is essentially unchanged, indicating that POT1a is not required for overhang protection. In contrast,
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49

Smith, Emmanuel W., Simon Lattmann, Zhehui Barry Liu, Bilal Ahsan, and Daniela Rhodes. "Insights into POT1 structural dynamics revealed by cryo-EM." PLOS ONE 17, no. 2 (2022): e0264073. http://dx.doi.org/10.1371/journal.pone.0264073.

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Анотація:
Telomeres are protein-DNA complexes that protect the ends of linear eukaryotic chromosomes. Mammalian telomeric DNA consists of 5′-(TTAGGG)n-3′ double-stranded repeats, followed by up to several hundred bases of a 3′ single-stranded G-rich overhang. The G-rich overhang is bound by the shelterin component POT1 which interacts with TPP1, the component involved in telomerase recruitment. A previously published crystal structure of the POT1 N-terminal half bound to the high affinity telomeric ligand 5′-TTAGGGTTAG-3′ showed that the first six nucleotides, TTAGGG, are bound by the OB1 fold, while th
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50

Liu, Jinqiang, Xichan Hu, Kehan Bao, et al. "The cooperative assembly of shelterin bridge provides a kinetic gateway that controls telomere length homeostasis." Nucleic Acids Research 49, no. 14 (2021): 8110–19. http://dx.doi.org/10.1093/nar/gkab550.

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Анотація:
Abstract Shelterin is a six-protein complex that coats chromosome ends to ensure their proper protection and maintenance. Similar to the human shelterin, fission yeast shelterin is composed of telomeric double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1 and Tpz1. The assembly of the proteinaceous Tpz1-Poz1-Rap1 complex occurs cooperatively and disruption of this shelterin bridge leads to unregulated telomere elongation. However, how this biophysical property of bridge assembly is integrated into shelterin function is not known. Here, utilizing
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