Inhibition telomere. Medical search. Frequent questions

Telomeres, the caps on the ends of eukaryotic chromosomes, play critical roles in cellular aging and cancer. (wikipedia.org)
The telomere-shelterin complexes that cap all eukaryotic chromosomes ensure that healthy cells can progress through the cell cycle by preventing the cellular DNA damage response from identifying chromosome ends as double-stranded breaks (DSBs). (wikipedia.org)
The first gapless, telomere-to-telomere (T2T) sequence assemblies of plant chromosomes were reported recently. (cas.cz)
Telomeres are repetitive noncoding DNA strands at the ends of eukaryotic (plants, animals, etc.) chromosomes. (sens.org)
The DNA still seemed to look normal, until the researchers focused on the caps that protect the ends of chromosomes, called telomeres. (labroots.com)
As normal cells age, the tips of their chromosomes, called telomeres, can start to break down, which is a signal for the cell to die. (drugtargetreview.com)
Telomerase expands the ends of chromosomes and protects telomeres from replication-dependent attrition, allowing cancer tumor cells to proliferate indefinitely by conquering the finish replication issue (3C5). (lavoixdesrroms.org)
The telomeres existing at the end of the eukaryotic chromosome, play an important role in localization, pairing of homologous chromosomes during cell division and synapsis formation, while telomerase is involved in maintenance of the telomere length. (openaccesspub.org)
Telomeres are repetitive DNA sequence of TTAGGG that, together with the protein shelterin complex, provide a protective cap at the end of our chromosomes [ 1 ]. (biomedcentral.com)
Telomerase repairs telomeres, which are segments at the end of chromosomes that shorten with each cell division. (stanete.com)

This may seem counter-intuitive, as short telomeres should activate the ATR/ATM DNA damage checkpoint and thereby prevent division. (wikipedia.org)
Resolving the question of why cancer cells have short telomeres led to the development of a two-stage model for how cancer cells subvert telomeric regulation of the cell cycle. (wikipedia.org)
Critically short telomeres activate cellular senescence or apoptosis, as mediated from the tumor suppressor p53, however in the lack of this checkpoint response, telomere dysfunction engenders chromosomal cancer and aberrations. (woofahs.com)
Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. (woofahs.com)
DC is an inherited disorder caused by abnormally short telomeres [ 23 ]. (prolekarniky.cz)

Telomere dysfunction promotes genomic instability and carcinogenesis via inappropriate end-to-end chromosomal rearrangements, or telomere fusions. (xstrahl.com)
Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, and cellular replication causes their loss. (nature.com)
Telomere, a complex of guanine-rich repeat sequences and associated proteins, caps and protects every eukaryotic chromosome end against chromosomal fusion, recombination, and terminal DNA degradation ( Blackburn, 2001 ). (nature.com)
Telomerase, a cellular reverse transcriptase, has been shown to maintain the chromosomal ends (telomeres) which allows for an unlimited cellular lifespan. (iu.edu)
Many correlative studies in human cancer and numerous other studies have supported the view that persistent DNA damage signaling resulting from telomere dysfunction provides pressure to deactivate critical checkpoints and sets the stage for 145525-41-3 manufacture accumulation of chromosomal aberrations and aneuploidy [15]. (woofahs.com)
Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. (nih.gov)

My project is to develop new high-throughput assays for quantifying activity of the Alternative Lengthening of Telomeres (ALT) pathway in human cells. (sens.org)

Telomerase, the enzyme capable of elongating telomeres, is usually restricted in human somatic cells, which contributes to progressive telomere shortening with cell-division and ageing. (biomedcentral.com)
This progressive telomere shortening is a mechanistic pathway involved in the aging process. (stanete.com)

As telomeres shorten as a natural consequence of repeated cell division or due to other factors, such as oxidative stress, shelterin proteins lose the ability to bind to telomeric DNA. (wikipedia.org)
Every time a cell divides, telomeres shorten, protecting the genetic material from being damaged and limiting the proliferation of the cell. (sens.org)

A recent study demonstrated the molecular basis of tetraploidization by deprotected telomeres in the absence of Pot1 and p53, further implicating dysfunctional telomeres as a cause of genomic instability in human cancer [16]. (woofahs.com)
Despite the large body of well-described biological outcomes, the molecular mechanisms underlying the role of p53 in suppressing the genomic instability associated with telomere dysfunction are not well understood. (woofahs.com)

Finally, we discuss how certain hallmarks of ageing (epigenetic alterations, mitochondrial dysfunction, telomere attrition, cellular senescence, and altered intercellular communication) predispose the ageing population to severe COVID-19. (ersjournals.com)

Numerous studies currently suggest that quadruplex formation in this overhang alters the structure and function of telomeres, inducing a damage response and rapid apoptosis in particular in cancer cells [ 14 - 24 ]. (hindawi.com)
Other cellular targets including Bak, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. (joplink.net)
Depletion of TIN2 causes profound telomere deprotection phenotypes including destabilization of the shelterin complex, activation of telomeric DNA damage signaling, and increased apoptosis [ 9 , 11 - 14 ]. (prolekarniky.cz)

To determine the clinical impact of these data, the researchers used a chemical enzyme inhibitor to cause telomere damage in several types of cancer cells, including lung cancer cells. (drugtargetreview.com)

However, there is evidence that inhibition of telomerase causes cancer cells to switch to the ALT pathway and continue maintaining telomere length. (sens.org)
The surviving cells become cancer cells, which are capable both of dividing indefinitely and maintaining telomere length (usually with the aid of telomerase). (actanaturae.ru)

The remainder maintain telomere length with ALT, a pathway based on homologous recombination (a mechanism used for DNA repair). (sens.org)
Mutations in shelterin components cause Dyskeratosis Congenita (DC) and related disease syndromes due to the inability to maintain telomere homeostasis. (prolekarniky.cz)

telomere dysfunction and Atm or p53 offers exposed opposing phenotypic outcomes upon lack of Atm versus p53 in the telomerase knockout mouse. (woofahs.com)
In this current study, we attempt to dissect the circuitry of the p53-mediated checkpoint response by analyzing transcriptional changes associated with telomere dysfunction. (woofahs.com)
Outcomes p53 reactivation in cells with telomere dysfunction causes powerful gene manifestation adjustments resembling a mobile checkpoint response To define the p53-mediated transcriptome MSH6 connected with telomere dysfunction, we used a era 4 telomerase-negative, Atm-negative (G4 (triple knockout, TKO) pores and skin fibroblasts display inactivation of mobile checkpoints offering genomic balance. (woofahs.com)

Telomerase can add telomeric repeats onto the chromosome ends, and prevents the replication-dependent loss of telomere and cellular senescence in highly proliferative cells of the germline and in the majority of cancers ( Blasco, 2005 ). (nature.com)
Protection of Drosophila chromosome ends through minimal telomere capping. (ens-lyon.fr)
The multi-subunit shelterin complexes bind along mammalian telomeres, shielding the natural chromosome ends from engaging the DNA damage signaling and repair machinery [ 1 ]. (prolekarniky.cz)

In somatic cells, the activity of telomerase, a reverse transcriptase that can elongate telomeric repeats, is usually diminished after birth so that the telomere length is gradually shortened with cell divisions, and triggers cellular senescence. (nature.com)
Finally, when researchers exposed in vitro cancer cells to the serum of the lifestyle group patients, they observed 8 times more cancer growth inhibition than the control group serum, suggesting that this treatment approach had significant effects at the cellular and molecular level. (kundaliniresearchinstitute.org)
Ogretmen 's group found that, when telomeres become damaged by age or in response to chemotherapy, p16 is a type of cellular decision-maker that helps cells decide to grow older or simply die. (drugtargetreview.com)
Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. (nih.gov)
Among the anti-aging benefits include inhibition of cellular senescense, reduced telomere reductions, and enhanced DNA repair. (geresdengle.com)

A critical length of telomere repeats is required to ensure proper telomere function and avoid the activation of DNA damage pathways that result in replicative senescence or cell death. (nature.com)
Telomerase is an enzyme that adds telomeric repeats to the ends of telomeres using a built-in template. (sens.org)
The telomeres consist of repeating sequences and a set of special proteins, which interact with these repeats and spatially organize them in a specific manner, resulting in the formation of the nucleoprotein complex known as telomeric heterochromatin [ 6 , 7 ]. (actanaturae.ru)
Among the shelterin components, TRF1 and TRF2 bind directly to duplex telomeric repeats [ 2 ], while POT1 binds to the single-stranded regions of telomeres [ 3 ]. (prolekarniky.cz)

Meanwhile, Rif2 and Rap1 inhibit NHEJ: knocking out Rif2 or Rap1 results in longer telomeres as measured by PCR, indicating that NHEJ occurred. (wikipedia.org)
Notably, mpeg1.1 + macrophages have much longer telomeres in the gut than in their haematopoietic tissue of origin, suggesting that there is modulation of telomerase in these cells, in the gut. (biomedcentral.com)

The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons. (mdpi.com)
In this context, a wide range of M-ATCUN derivatives have been designed purposefully for various redox- and non-redox-based applications, including spectroscopic probes, target-based catalytic metallodrugs, inhibition of amyloid-beta toxicity, and telomere shortening, enzyme inactivation, biomolecules stitching or modification, next-generation antibiotic, and small molecule activation. (unl.pt)

Together, these experiments define a novel requirement for 53BP1 in the fusions of DNA-PKcs-deficient telomeres throughout the cell cycle and uncover a Ligase IV-independent, PARP1-dependent pathway that fuses telomeres at reduced efficiency in the absence of 53BP1. (xstrahl.com)
These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway. (joplink.net)

This loss of inhibition is one reason why telomere shortening causes senescence (Figure 1B). (wikipedia.org)
11 Imad Naasani,Hiroyudi Seimiya.Telomer asae inhibition,telomere shortening,and senescence of cancer cells by tea catechins J .Biochemical and Biophysical Res earch Commnications,1998,249:391 396. (100md.com)
It was also shown that inhibition of the p16 tumour suppressor gene delays growth arrest and therefore senescence of MSC [ 16 ]. (hindawi.com)
Telomere shortening leads to the attainment of the Hayflick limit, the transition of cells to a state of senescence. (actanaturae.ru)
Inhibition of telomerase network marketing leads to telomere harm, following senescence, and tumor suppression (8C11). (lavoixdesrroms.org)

We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy. (woofahs.com)

Using mouse embryonic fibroblasts lacking 53BP1 and/or DNA-PKcs, we show that 53BP1 deficiency suppresses G1-generated telomere fusions that normally accumulate in DNA-PKcs-deficient fibroblasts with passage. (xstrahl.com)
Thus, telomerase activity and telomere maintenance are associated with the immortality of cancer cells, germ-line cells, and embryonic stem (ES) cells. (nature.com)

When telomeres reach a critically short length, sufficient shelterin proteins to inhibit checkpoint activation are not available, although NHEJ and HR generally remain inhibited at this point. (wikipedia.org)
Previous work indicates that the DNA Damage Response (DDR) factor 53BP1 promotes the fusion of telomeres rendered dysfunctional by loss of TRF2, but is dispensable for the fusion of telomeres lacking Pot1 or critically shortened (in telomerase-deficient mice). (xstrahl.com)

Inhibition of nickel nanoparticles-induced toxicity by epigallocatechin-3-gallate in JB6 cells may be through down-regulation of the MAPK signaling pathways. (cdc.gov)

Thus, even in stem cells, except for embryonal stem cells and cancer stem cells, telomere shortening occurs during replicative ageing, possibly at a slower rate than that in normal somatic cells. (nature.com)
In most human somatic cells except for stem cells and lymphocytes, telomerase activity is diminished after birth so that telomere length shortens with each cell division. (nature.com)
Telomerase, the reverse transcriptase capable of elongating telomeres, is mostly restricted in somatic cells. (biomedcentral.com)

Depletion of TPP1 or POT1 results in the deregulation of the single-stranded telomeric terminal overhang and the induction of a DNA damage response at telomeres [ 5 - 7 ]. (prolekarniky.cz)

Here, we examine a role for 53BP1 at telomeres rendered dysfunctional by loss or catalytic inhibition of DNA-PKcs. (xstrahl.com)

This problem makes eukaryotic cells unable to copy the last few bases on the 3' end of the template DNA strand, leading to chromosome-and, therefore, telomere-shortening every S phase. (wikipedia.org)
Measurements of telomere lengths across cell types at various ages suggest that this gradual chromosome shortening results in a gradual reduction in telomere length at a rate of approximately 25 nucleotides per year. (wikipedia.org)
Conversely, inhibition of telomerase in cancer cells results in telomere shortening, reduction of cell growth, tumor formation, and metastases in vitro and in vivo. (iu.edu)
The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. (joplink.net)
The shortening of telomeres constitutes an intrinsic factor, whereas DNA damage is considered an extrinsic factor. (hindawi.com)
Stem cells are characterized by a lower telomerase activity, which enables only partial compensation for the shortening of telomeres. (actanaturae.ru)
Importantly, this is accompanied by telomere shortening and DNA damage responses with ageing and a telomerase-dependent decrease in expression of autophagy and immune activation markers. (biomedcentral.com)
Telomerase expression is also a hallmark of tissue stem cells, but its expression in these cells is still insufficient to completely prevent telomere shortening over time [ 11 ]. (biomedcentral.com)
This shortening of the telomere is due to external factors, such as tobacco consumption (RAY et al . (bvsalud.org)

As stem cells have elongated proliferative capacity, they should have a mechanism that maintains telomere length through many cell divisions. (nature.com)
The telomerase recruitment defect conferred by TIN2-R282H is likely through a mechanism independent of TIN2's role in anchoring TPP1 at telomeres, since TPP1 localization to telomeres is unaffected by the mutation. (prolekarniky.cz)

Likewise, we find that 53BP1 promotes telomere fusions during the replicative phases of the cell cycle in cells treated with the specific DNA-PKcs inhibitor NU7026. (xstrahl.com)
We found that Akt inhibition did not compromise CD19CAR T cell proliferation and expansion in vitro, independent of the T cell subsets, as comparable CD19CAR T cell expansion was observed after culturing in the presence or absence of Akt inhibitor. (biomedcentral.com)
The inhibitor, ABC294640, prevents cancer cells from protecting their telomeres, by inhibiting an enzyme called sphingosine kinase 2. (drugtargetreview.com)

The two major protein complexes that bind to telomeric DNA in S. cerevisiae are: the Cdc13-Stn1-Ten1 (CST) complex, which binds the single-stranded DNA (ssDNA) of the 3' G-rich overhang at the end of the telomere, and the Rif1-Rif2-Rap1 complex, which binds the double-stranded DNA (dsDNA) preceding the 3' overhang. (wikipedia.org)

TER is a non-coding RNA, and it contains the region which serves as a template for telomere synthesis. (actanaturae.ru)
Telomerase consists of two major components: reverse transcriptase (TERT) and telomerase RNA (TER), which contains the template domain for the telomere repeat synthesis [ 9 ]. (actanaturae.ru)

Analogously, proteins that bind to human telomeres as part of the shelterin complex enable cell cycle progress and prevent erroneous DSB repair. (wikipedia.org)
The shelterin complex protects telomeres from being processed by the DNA damage repair machinery, and also regulates telomerase access and activity at telomeres. (prolekarniky.cz)
Increasing evidence suggests that the shelterin complex also regulates access of telomerase to telomeres and hence telomerase action on them. (prolekarniky.cz)

Thus, our data claim that S1P binding to hTERT mimicks phosphorylation allosterically, marketing telomerase balance and telomere maintenance therefore, cell proliferation, and tumor development INTRODUCTION Individual telomerase can be an RNA-dependent DNA polymerase which has a catalytic element, hTERT (individual telomerase invert transcriptase), and an interior RNA template, TR (1, 2). (lavoixdesrroms.org)

To prevent degradation by exonucleases or processing as damaged DNA, the telomere 3′ single-strand overhang folds back into the D-loop of duplex telomeric DNA to form a protective 'T-loop', which is reinforced with TRF2 and other telomeric DNA-binding proteins named Shelterin ( de Lange, 2005 ). (nature.com)

Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. (elifesciences.org)
Since the DSB ends undergo nucleolytic degradation (resection) of their 5′-ending strands, we investigated the contribution of resection in this DSB-induced transcriptional inhibition. (elifesciences.org)
Furthermore, Rad9 and generation of γH2A reduce this DSB-induced transcriptional inhibition by counteracting DSB resection. (elifesciences.org)

His PhD is in Telomere Biology, Telomerase inhibition and the radiosensitivity of Head and Neck Cancer. (bradford.ac.uk)
Life Length is the leader in telomere biology also offering additional solutions for clinical/preclinical studies as well as drug discovery. (lifelength.com)

these sequences were referred to as telomeres [ 3-5 ]. (actanaturae.ru)
Later on it was suggested the potential LaGT2 focuses on may not be restricted to telomere sequences [14]. (healthandwellnesssource.org)

Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. (nih.gov)

First, the DNA damage checkpoint must be inactivated to allow cells to continue dividing even when telomeres pass the critical length threshold. (wikipedia.org)
The regulation of telomere length and telomerase activity is a complex and dynamic process that is tightly linked to cell cycle regulation in human stem cells. (nature.com)
Telomerase is an enzyme that maintains the length of the telomere. (actanaturae.ru)
The telomere length specifies the number of divisions a cell can undergo before it finally dies (i.e. the proliferative potential of cells). (actanaturae.ru)
Background: There is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer's disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. (mdpi.com)
Results: Lithium resulted in 120% (2 mM), 180% (0.2 mM) and 140% (0.02 mM) increments in telomere length as compared to untreated controls. (mdpi.com)
Oxidative stress, DNA methylation, and telomere length changes in peripheral blood mononuclear cells after pulmonary exposure to metal-rich welding nanoparticles. (cdc.gov)
One of the causes linked to DS is the biological age of the mother and a marked decrease in the telomere length of the woman who gives birth to a child with DS. (bvsalud.org)

The only shelterin subunit known to promote telomerase function is TPP1, which mediates telomerase recruitment to telomeres and stimulates telomerase processivity. (prolekarniky.cz)

We now know those structures are very relevant to many critical biological processes like gene regulation, expression of telomerase and telomere maintenance, understanding of growth/oncogenes like C-myc, understanding of organismic development, comprehension of certain enigmatic diseases like ALS and possible new cancer treatments. (anti-agingfirewalls.com)

Second, to survive after disabling the DNA damage checkpoint, precancerous cells must activate mechanisms to extend their telomeres. (wikipedia.org)
Telomere Maintenance Mechanisms. (sens.org)
4 Okabe S,Suganuma M,Hayashi M,et al.Mechanisms of growth inhibition of human lung cancer cell line,PC 9,by tea polyphenols J .Jpn J Cancer Res,1997,88(7):639 643. (100md.com)

Intellectual disability-associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM-mediated chromatin deposition of histone H3.3. (ens-lyon.fr)

An important facet to how telomeres function in these roles is their involvement in cell cycle regulation. (wikipedia.org)
Basically, given the difference of telomere and telomerase activity in human and mouse cells, the telomere and telomerase status in stem cell populations is different between humans and mice ( Harrington, 2004 ). (nature.com)
Functionally, Akt inhibition did not dampen cell-mediated effector function, while Th1 cytokine production increased. (biomedcentral.com)
Inhibition of Akt signaling during ex vivo priming and expansion gives rise to CD19CAR T cell populations that display comparatively higher antitumor activity. (biomedcentral.com)
As a result of this enzyme inhibition, telomeres were damaged, resulting in cancer cell death when p16 levels were low or absent. (drugtargetreview.com)

The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. (nih.gov)

Almost all cancer cells have shortened telomeres. (wikipedia.org)
Some cells, such as stem cells and cancer cells, are able to lengthen their telomeres to be able to divide without limit. (sens.org)
85% of cancer cells use the enzyme telomerase to lengthen telomeres. (sens.org)
There is a continuous need for new biomarkers for diseases like cancer, cardiovascular, Alzheimer's and other age-related pathologies to which telomeres are directly related and are being used as a powerful tool. (lifelength.com)
The research lab of Brittney-Shea Herbert, PhD studies the roles of telomeres and telomerase in aging and cancer. (iu.edu)
However, cancer cells have developed a way to prevent their telomeres from falling apart, which helps them to live much longer than normal cells. (drugtargetreview.com)
Ogretmen 's research group have discovered a specific way that cancer cells escape death in response to telomere damage. (drugtargetreview.com)

We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model. (biomedcentral.com)

However, telomere fusions are not fully abrogated in DNA-PKcs-inhibited 53BP1-deficient cells, but occur with a frequency approximately 10-fold lower than in control 53BP1-proficient cells. (xstrahl.com)
Recently, the importance of telomere maintenance in human stem cells has been highlighted by studies on dyskeratosis congenital, which is a genetic disorder in the human telomerase component. (nature.com)
Here we review the role of telomeres and telomerase in the function and capacity of the human stem cells. (nature.com)
The researchers found that p16 became most important to cells when their telomeres began to break down. (drugtargetreview.com)

Here, I will assume that you are already familiar with telomeres and the general function of telomerase. (antiaging-systems.com)
In any case, I will discuss the supplements, nutrients and strategies that can help improve the overall function of telomerase and so result in healthy telomeres, and thus, healthy DNA. (antiaging-systems.com)
In this study, we have identified TIN2-R282H, the most common DC-causing mutation in shelterin subunit TIN2, as a separation-of-function mutant which impairs telomerase recruitment to telomeres, but not chromosome end protection. (prolekarniky.cz)
Depletion of TIN2, which associates with TPP1, leads to reduced levels of TPP1-mediated telomerase association to telomeres [ 19 ], although this result might simply reflect an indirect function for TIN2 as a regulator of telomerase recruitment through anchoring TPP1 at telomeres. (prolekarniky.cz)

Anatomy5

Organisms3

Diseases5

Chemicals and Drugs16

Analytical, Diagnostic and Therapeutic Techniques and Equipment2

Phenomena and Processes18

Information Science2

Chromosomes10

Short telomeres5

Chromosomal6

Alternative Lengtheni1

Progressive telomere2

Shorten2

Genomic instability2

Attrition1

Apoptosis3

Cause Telomere Damage1

Maintaining telomere length2

Maintain telomere2

Dysfunction3

Chromosome ends3

Cellular5

Repeats4

Longer telomeres2

Amyloid-beta2

Pathway2

Senescence5

Recombination1

Embryonic2

Critically2

Toxicity1

Somatic cells3

Pot11

Dysfunctional1

Shortening9

Mechanism2

Inhibitor3

Rif21

Synthesis2

Shelterin complex3

Catalytic1

Overhang1

Transcriptional3

Biology2

Sequences2

Ends1

Length8

Mediates1

Oncogenes1

Mechanisms3

Gene expression1

Cell5

Protein1

Cancer7

Activity1

Cells4

Function4