An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.
A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
A species of ciliate protozoa used in genetic and cytological research.
A genus of ciliate protozoa having a dorsoventrally flattened body with widely spaced rows of short bristle-like cilia on the dorsal surface.
The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING.
A genus of ciliate protozoa commonly used in genetic, cytological, and other research.
Catalytically active enzymes that are formed by the combination of an apoenzyme (APOENZYMES) and its appropriate cofactors and prosthetic groups.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 2 in that it contains acidic N-terminal amino acid residues.
Ribonucleic acid in protozoa having regulatory and catalytic roles as well as involvement in protein synthesis.
A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. EC 2.7.7.31.
A distinct subnuclear domain enriched in splicesomal snRNPs (RIBONUCLEOPROTEINS, SMALL NUCLEAR) and p80-coilin.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15)
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A cell line derived from cultured tumor cells.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.
A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
An ascomycetous yeast of the fungal family Saccharomycetaceae, order SACCHAROMYCETALES.
A group of telomere associated proteins that interact with TRF1 PROTEIN, contain ANKYRIN REPEATS and have poly(ADP-ribose) polymerase activity.
A genus of ciliate protozoa having a unique cursorial type of locomotion.
A unique DNA sequence of a replicon at which DNA REPLICATION is initiated and proceeds bidirectionally or unidirectionally. It contains the sites where the first separation of the complementary strands occurs, a primer RNA is synthesized, and the switch from primer RNA to DNA synthesis takes place. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
The real or apparent movement of objects through the visual field.
The process by which a DNA molecule is duplicated.
The terms, expressions, designations, or symbols used in a particular science, discipline, or specialized subject area.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The unsuccessful attempt to kill oneself.
A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm.

Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. (1/3684)

The telomerase reverse transcriptase component (TERT) is not expressed in most primary somatic human cells and tissues, but is upregulated in the majority of immortalized cell lines and tumors. Here, we identify the c-Myc transcription factor as a direct mediator of telomerase activation in primary human fibroblasts through its ability to specifically induce TERT gene expression. Through the use of a hormone inducible form of c-Myc (c-Myc-ER), we demonstrate that Myc-induced activation of the hTERT promoter requires an evolutionarily conserved E-box and that c-Myc-ER-induced accumulation of hTERT mRNA takes place in the absence of de novo protein synthesis. These findings demonstrate that the TERT gene is a direct transcriptional target of c-Myc. Since telomerase activation frequently correlates with immortalization and telomerase functions to stabilize telomers in cycling cells, we tested whether Myc-induced activation of TERT gene expression represents an important mechanism through which c-Myc acts to immortalize cells. Employing the rat embryo fibroblast cooperation assay, we show that TERT is unable to substitute for c-Myc in the transformation of primary rodent fibroblasts, suggesting that the transforming activities of Myc extend beyond its ability to activate TERT gene expression and hence telomerase activity.  (+info)

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. (2/3684)

Telomerase is a ribonucleoprotein enzyme that adds hexanucleotide repeats TTAGGG to the ends of chromosomes. Telomerase activation is known to play a crucial role in cell-immortalization and carcinogenesis. Telomerase is shown to have a correlation with cell cycle progression, which is controlled by the regulation of cyclins, cyclin dependent kinases (cdks) and cyclin dependent kinase inhibitors (cdkis). Abnormal expression of these regulatory molecules may cause alterations in cell cycle with uncontrolled cell growth, a universal feature of neoplasia. Skin cancer is the most prevalent form of cancer in humans and the solar UV radiation is its major cause. Here, we investigated modulation in telomerase activity and protein expression of cell cycle regulatory molecules during the development of UVB-induced tumors in SKH-1 hairless mice. The mice were exposed to 180 mjoules/cm2 UVB radiation, thrice weekly for 24 weeks. The animals were sacrificed at 4 week intervals and the studies were performed in epidermis. Telomerase activity was barely detectable in the epidermis of non-irradiated mouse. UVB exposure resulted in a progressive increase in telomerase activity starting from the 4th week of exposure. The increased telomerase activity either persisted or further increased with the increased exposure. In papillomas and carcinomas the enzyme activity was comparable and was 45-fold higher than in the epidermis of control mice. Western blot analysis showed an upregulation in the protein expression of cyclin D1 and cyclin E and their regulatory subunits cdk4 and cdk2 during the course of UVB exposure and in papillomas and carcinomas. The protein expression of cdk6 and ckis viz. p16/Ink4A, p21/Waf1 and p27/Kip1 did not show any significant change in UVB exposed skin, but significant upregulation was observed both in papillomas and carcinomas. The results suggest that telomerase activation may be involved in UVB-induced tumorigenesis in mouse skin and that increased telomerase activity may be associated with G1 phase of the cell cycle.  (+info)

Telomerase activity is sufficient to allow transformed cells to escape from crisis. (3/3684)

The introduction of simian virus 40 large T antigen (SVLT) into human primary cells enables them to proliferate beyond their normal replicative life span. In most cases, this temporary escape from senescence eventually ends in a second proliferative block known as "crisis," during which the cells cease growing or die. Rare immortalization events in which cells escape crisis are frequently correlated with the presence of telomerase activity. We tested the hypothesis that telomerase activation is the critical step in the immortalization process by studying the effects of telomerase activity in two mortal SVLT-Rasval12-transformed human pancreatic cell lines, TRM-6 and betalox5. The telomerase catalytic subunit, hTRT, was introduced into late-passage cells via retroviral gene transfer. Telomerase activity was successfully induced in infected cells, as demonstrated by a telomerase repeat amplification protocol assay. In each of nine independent infections, telomerase-positive cells formed rapidly dividing cell lines while control cells entered crisis. Telomere lengths initially increased, but telomeres were then maintained at their new lengths for at least 20 population doublings. These results demonstrate that telomerase activity is sufficient to enable transformed cells to escape crisis and that telomere elongation in these cells occurs in a tightly regulated manner.  (+info)

Analysis of genomic integrity and p53-dependent G1 checkpoint in telomerase-induced extended-life-span human fibroblasts. (4/3684)

Life span determination in normal human cells may be regulated by nucleoprotein structures called telomeres, the physical ends of eukaryotic chromosomes. Telomeres have been shown to be essential for chromosome stability and function and to shorten with each cell division in normal human cells in culture and with age in vivo. Reversal of telomere shortening by the forced expression of telomerase in normal cells has been shown to elongate telomeres and extend the replicative life span (H. Vaziri and S. Benchimol, Curr. Biol. 8:279-282, 1998; A. G. Bodnar et al., Science 279:349-352, 1998). Extension of the life span as a consequence of the functional inactivation of p53 is frequently associated with loss of genomic stability. Analysis of telomerase-induced extended-life-span fibroblast (TIELF) cells by G banding and spectral karyotyping indicated that forced extension of the life span by telomerase led to the transient formation of aberrant structures, which were subsequently resolved in higher passages. However, the p53-dependent G1 checkpoint was intact as assessed by functional activation of p53 protein in response to ionizing radiation and subsequent p53-mediated induction of p21(Waf1/Cip1/Sdi1). TIELF cells were not tumorigenic and had a normal DNA strand break rejoining activity and normal radiosensitivity in response to ionizing radiation.  (+info)

Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. (5/3684)

Activation of telomerase is one of the rate-limiting steps in human cell immortalization and carcinogenesis Human telomerase is composed of at least two protein subunits and an RNA component. Regulation of expression of the catalytic subunit, human telomerase reverse transcriptase (hTERT), is suggested as the major determinant of the enzymatic activity. We report here the cloning and characterization of the 5'-regulatory region of the hTERT gene. The highly GC-rich content of the 5' end of the hTERT cDNA spans to the 5'-flanking region and intron 1, making a CpG island. A 1.7-kb DNA fragment encompassing the hTERT gene promoter was placed upstream of the luciferase reporter gene and transiently transfected into human cell lines of fibroblastic and epithelial origins that differed in their expression of the endogenous hTERT gene. Endogenous hTERT-expressing cells, but not nonexpressing cells, showed high levels of luciferase activity, suggesting that the regulation of hTERT gene expression occurs mainly at the transcriptional level. Additional luciferase assays using a series of constructs containing unidirectionally deleted fragments revealed that a 59-bp region (-208 to -150) is required for the maximal promoter activity. The region contains a potential Myc oncoprotein binding site (E-box), and cotransfection of a c-myc expression plasmid markedly enhanced the promoter activity, suggesting a role of the Myc protein in telomerase activation. Identification of the regulatory regions of the hTERT promoter sequence will be essential in understanding the molecular mechanisms of positive and negative regulation of telomerase.  (+info)

A telomere-independent senescence mechanism is the sole barrier to Syrian hamster cell immortalization. (6/3684)

Reactivation of telomerase and stabilization of telomeres occur simultaneously during human cell immortalization in vitro and the vast majority of human cancers possess high levels of telomerase activity. Telomerase repression in human somatic cells may therefore have evolved as a powerful resistance mechanism against immortalization, clonal evolution and malignant progression. The comparative ease with which rodent cells immortalize in vitro suggests that they have less stringent controls over replicative senescence than human cells. Here, we report that Syrian hamster dermal fibroblasts possess substantial levels of telomerase activity throughout their culture life-span, even after growth arrest in senescence. In our studies, telomerase was also detected in uncultured newborn hamster skin, in several adult tissues, and in cultured fibroblasts induced to enter the post-mitotic state irreversibly by serum withdrawal. Transfection of near-senescent dermal fibroblasts with a selectable plasmid vector expressing the SV40 T-antigen gene resulted in high-frequency single-step immortalization without the crisis typically observed during the immortalization of human cells. Collectively, these data provide an explanation for the increased susceptibility of rodent cells to immortalization (and malignant transformation) compared with their human equivalents, and provide evidence for a novel, growth factor-sensitive, mammalian senescence mechanism unrelated to telomere maintenance.  (+info)

Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. (7/3684)

To study the effect of continued telomere shortening on chromosome stability, we have analyzed the telomere length of two individual chromosomes (chromosomes 2 and 11) in fibroblasts derived from wild-type mice and from mice lacking the mouse telomerase RNA (mTER) gene using quantitative fluorescence in situ hybridization. Telomere length at both chromosomes decreased with increasing generations of mTER-/- mice. At the 6th mouse generation, this telomere shortening resulted in significantly shorter chromosome 2 telomeres than the average telomere length of all chromosomes. Interestingly, the most frequent fusions found in mTER-/- cells were homologous fusions involving chromosome 2. Immortal cultures derived from the primary mTER-/- cells showed a dramatic accumulation of fusions and translocations, revealing that continued growth in the absence of telomerase is a potent inducer of chromosomal instability. Chromosomes 2 and 11 were frequently involved in these abnormalities suggesting that, in the absence of telomerase, chromosomal instability is determined in part by chromosome-specific telomere length. At various points during the growth of the immortal mTER-/- cells, telomere length was stabilized in a chromosome-specific man-ner. This telomere-maintenance in the absence of telomerase could provide the basis for the ability of mTER-/- cells to grow indefinitely and form tumors.  (+info)

Induction of telomerase activity in v-myc-transformed avian cells. (8/3684)

Telomerase activity is detectable in the majority of tumors or immortalized cell lines, but is repressed in most normal human somatic cells. It is generally assumed that reactivation of telomerase prevents the erosion of chromosome ends which occurs in cycling cells and, hence, hinders cellular replicative senescence. Here, we show that the expression of v-Myc oncoprotein by retroviral infection of telomerase-negative embryonal quail myoblasts and chicken neuroretina cells is sufficient for reactivating telomerase activity, earlier than telomere shortening could occur. Furthermore, the use of a conditional v-Myc-estrogen receptor protein (v-MycER) causes estrogen-dependent expression of detectable levels of telomerase activity in recently infected chick embryo fibroblasts and neuroretina cells. We conclude that the high levels of telomerase activity in v-Myc-expressing avian cells are not the mere consequence of transformation or of a differentiative block, since v-Src tyrosine kinase, which prevents terminal differentiation and promotes cell transformation, fails to induce telomerase activity.  (+info)

Telomerase activity is involved in telomere length maintenance. Leukocytes, unlike many human somatic tissues, have detectable telomerase activity. These cells provide a normal human cell type in which to study telomerase. We studied the regulation of telomerase activity and the telomerase RNA component as leukocytes were stimulated to enter the cell cycle. In primary human leukocytes stimulated with phytohemagglutinin, telomerase activity increased , 10-fold as naturally quiescent cells entered the cell cycle. Antibodies to the T cell receptor (TCR)/CD3 complex and the costimulatory CD28 receptor induced telomerase activity in a T cell-enriched population of cells. Rapamycin, an immunosuppressant that blocks TCR/CD3 signal transduction pathways and cdk2 activation, blocked telomerase induction. Hydroxyurea, an inhibitor of S phase, did not block cdk2 kinase activity or telomerase activation. In summary, telomerase is regulated in G1 phase as normal human T cells enter the cell cycle.. ...
Telomerase is a reverse transcriptase that adds telomeric repeats (TTAGGG)n to chromosomal ends, compensating for the telomere shortening that occurs with DNA replication. In normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to limited lifespan and senescence. Reactivation of telomerase activity is associated with human cancer and cell immortalization. Approximately 85% of human cancers, including breast, prostate, stomach, bladder, colon, and liver cancer, have telomerase activity, whereas most normal somatic cells do not. The specificity of telomerase to human cancer has led to investigations of telomerase activity and expression as a tumor marker. For example, the presence of telomerase activity in human urine has been identified as a marker for human bladder carcinoma. Human telomerase consists of three major subunits: a catalytic protein subunit called hTERT (for human TElomerase Reverse Transcriptase), a template RNA called hTR, and telomerase
Mutations in the gene for telomerase reverse transcriptase (hTERT) are associated with diseases including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis and cancer. Understanding the molecular basis of these telomerase-associated diseases requires dependable quantitative measurements of telomerase enzyme activity. Furthermore, recent findings that the human POT1-TPP1 chromosome end-binding protein complex stimulates telomerase activity and processivity provide incentive for testing variant telomerases in the presence of these factors. In the present work, we compare multiple disease-associated hTERT variants reconstituted with the RNA subunit hTR in two systems (rabbit reticulocyte lysates and human cell lines) with respect to telomerase enzymatic activity, processivity and activation by telomere proteins. Surprisingly, many of the previously reported disease-associated hTERTalleles give near-normal telomerase enzyme activity. It is possible that a small deficit in telomerase activity is
Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT-PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative ...
TY - JOUR. T1 - The 58-kDa microspherule protein (MSP58) represses human telomerase reverse transcriptase (hTERT) gene expression and cell proliferation by interacting with telomerase transcriptional element-interacting factor (TEIF). AU - Hsu, Che Chia. AU - Chen, Chang Han. AU - Hsu, Tsung I.. AU - Hung, Jan Jong. AU - Ko, Jiunn Liang. AU - Zhang, Bo. AU - Lee, Yi Chao. AU - Chen, Han Ku. AU - Chang, Wen Chang. AU - Lin, Ding Yen. PY - 2014/3. Y1 - 2014/3. N2 - 58-kDa microspherule protein (MSP58) plays an important role in a variety of cellular processes including transcriptional regulation, cell proliferation and oncogenic transformation. Currently, the mechanisms underlying the oncogenic effect of MSP58 are not fully understood. The human telomerase reverse transcriptase (hTERT) gene, which encodes an essential component for telomerase activity that is involved in cellular immortalization and transformation, is strictly regulated at the gene transcription level. Our previous study revealed ...
TY - JOUR. T1 - High-throughput analysis of telomerase by capillary electrophoresis. AU - Atha, Donald H.. AU - Miller, Karen. AU - Sanow, Anita D.. AU - Xu, Jingfan. AU - Hess, Jennifer L.. AU - Wu, Osmond C.. AU - Wang, Wendy. AU - Srivastava, Sudhir. AU - Highsmith, W. Edward. PY - 2003/1. Y1 - 2003/1. N2 - The enzyme telomerase is expressed in (85-90)% of all human cancers, but not in normal, non-stem cell somatic tissues. Clinical assays for telomerase in easily obtained body fluids would have great utility as noninvasive, cost-effective methods for the early detection of cancer. The most commonly used method for the detection and quantification of telomerase enzyme activity is the polymerase chain reaction (PCR)-based assay known as the telomerase repeat amplification protocol or TRAP assay. Most of the TRAP assay systems use a slab-gel based electrophoresis system to size and quantify the PCR-amplified extension products. We are developing high-throughput capillary electrophoresis (CE) ...
Human telomerase reverse transcriptase (hTERT) underlies cancer cell immortalization, and the expression of hTERT is regulated strictly at the gene transcription. Here, we report that transcription factor Ets2 is required for hTERT gene expression and breast cancer cell proliferation. Silencing Ets2 induces a decrease of hTERT gene expression and increase in human breast cancer cell death. Reconstitution with recombinant hTERT rescues the apoptosis induced by Ets2 depression. In vitro and in vivo analyses show that Ets2 binds to the EtsA and EtsB DNA motifs on the hTERT gene promoter. Mutation of either Ets2 binding site reduces the hTERT promoter transcriptional activity. Moreover, Ets2 forms a complex with c-Myc as demonstrated by co-immunoprecipitation and glutathione S-transferase pulldown assays. Immunological depletion of Ets2, or mutation of the EtsA DNA motif, disables c-Myc binding to the E-box, whereas removal of c-Myc or mutation of the E-box also compromises Ets2 binding to EtsA. ...
The mechanism of telomere elongation by telomerase. In this example the telomerase enzyme is synthesizing the repeated sequence TTGGGG, which is the telomeric sequence of Tetrahymena thermophila.. The first detection of telomerase activity, in the ciliateTetrahymena thermophila, was followed by its detection in a variety of organisms including vertebrates, yeast, and plants. In the absence of telomerase activity, telomeres shorten with each cell division. Normal human somatic cells lack detectable telomerase activity, whereas telomerase is activated in germ cells, immortalized cells and the majority of primary tumors. The correlation between telomerase activity and tumor growth has spurred investigations of the possiblities to use telomerase activity as a target for anticancer drug treatments.. Our identification of much longer telomeric repeat units (16-26 bp) in several yeast species has expanded the previous range of telomeric repeat sequences to include not only more complex sequences, but ...
Background: Iron is an essential trace element in cell proliferation. Several investigations demonstrate that iron deprivation inhibits cell proliferation. However, the impact of iron on telomerase activity of activated lymphocytes remains unexplained to date. Objective: In this study, the effect of iron on the proliferation and telomerase activity of lymphocytes stimulated by phytohemagglutinin (PHA) were investigated. Methods: Iron loading was performed by incubating peripheral blood mononuclear cells in 500μM FeSO4.7H2O for 24 h and iron chelation was done by exposing cells to desferrioxamine, a potent iron chelator. The effects of silymarin, a flavonoid with both antioxidant and iron chelating activities, on the proliferation and telomerase activity of PHAactivated lymphocytes were also compared with desferrioxamine. Proliferation and telomerase activity were assessed using BrdU incorporation assay and Telomeric Repeat Amplification Protocol (TRAP), respectively. Results: The proliferations of
Telomerase, a ribonucleoprotein with reverse transcriptase activity, enables human cells to maintain chromosomal stability and to proliferate without limits. Various stud..
TY - JOUR. T1 - Stabilization of telomere length and karyotypic stability are directly correlated with the level of hTERT gene expression in primary fibroblasts. AU - Cui, Wei. AU - Aslam, Samena. AU - Fletcher, Judy. AU - Wylie, Diana. AU - Clinton, Michael. AU - Clark, A John. PY - 2002. Y1 - 2002. N2 - Telomere shortening and lack of telomerase activity have been implicated in cellular senescence in human fibroblasts. Expression of the human telomerase (hTERT) gene in sheep fibroblasts reconstitutes telomerase activity and extends their lifespan. However, telomere length is not maintained in all cell lines, even though in vitro telomerase activity is restored in all of them. Cell lines expressing higher levels of hTERT mRNA do not exhibit telomere erosion or genomic instability. By contrast, fibroblasts expressing lower levels of hTERT do exhibit telomere shortening, although the telomeres eventually stabilize at a shorter length. The shorter telomere lengths and the extent of karyotypic ...
Telomere dysfunction-induced loss of genome integrity and its associated DNA damage signaling and checkpoint responses are well-established drivers that cause tissue degeneration during ageing. Cancer, with incidence rates greatly increasing with age, is characterized by short telomere lengths and high telomerase activity. To study the roles of telomere dysfunction and telomerase reactivation in ageing and cancer, the protocol shows how to generate two murine inducible telomerase knock-in alleles 4-Hydroxytamoxifen (4-OHT)-inducible TERT-Estrogen Receptor (mTERT-ER) and Lox-Stopper-Lox TERT (LSL-mTERT). The protocol describes the procedures to induce telomere dysfunction and reactivate telomerase activity in mTERT-ER and LSL-mTERT mice in vivo. The representative data show that reactivation of telomerase activity can ameliorate the tissue degenerative phenotypes induced by telomere dysfunction. In order to determine the impact of telomerase reactivation on tumorigenesis, we generated prostate ...
Telomerase is a unique reverse transcriptase that replicates the telomeric DNA at most eukaryotic chromosomal ends. The telomerase consists of the catalytic protein subunit TERT and the RNA component TR that provides the template for telomeric DNA synthesis. In vitro reconstitution of telomerase core components in large quantity is the prerequisite to studying the catalytic mechanisms of telomerase at the structural level; however, large-scale preparation of recombinant telomerase, especially that of higher eukaryotes, has been a big challenge for a long time. It has been known that the CR4/5 domain of the vertebrate TR binds to the TRBD domain of TERT and the interaction is essential to the assembly and enzymatic activity of telomerase. We assembled the TRBD-CR4/5 ribonucleoprotein complex of the medaka fish telomerase in vitro and determined its atomic structure through X-ray crystallography. Our study provides the structural insight into the RNA-protein recognition mechanism that is common to most
Eukaryotic cells undergo chromosome shortening during each cell division due to the inability of DNA polymerase to replicate chromosome ends. This end replication problem is counteracted by the ribonucleoprotein telomerase, which functions as a reverse transcriptase to add DNA repeats to chromosome ends. These DNA repeats, called telomeres, delay cellular senescence and recruit DNA binding proteins which protect chromosome ends and distinguish them from double-strand breaks. Telomere attrition is thought to function as a means of tumor suppression as cells can only undergo a limited number of divisions in the absence of telomerase or an alternative mechanism for replenishing DNA at chromosome ends. In multicellular organisms, telomerase is present and active during the early stages of development, but is later downregulated, resulting in little or no activity in most somatic cell types. In contrast, approximately 90% of cancer cells do have detectable telomerase activity. This discovery has ...
TY - JOUR. T1 - Telomerase promoter reprogramming and interaction with general transcription factors in the human mesenchymal stem cell. AU - Serakinci, Nedime. AU - Hoare, Stacey F.. AU - Kassem, Moustapha. AU - Atkinson, Stuart P.. AU - Keith, W. Nicol. PY - 2006/1/1. Y1 - 2006/1/1. N2 - The human adult mesenchymal stem cell (hMSC) does not express telomerase and has been shown to be the target for neoplastic transformation after transduction with hTERT. These findings lend support to the stem cell hypothesis of cancer development but by supplying hTERT, the molecular events required to upregulate hTERT expression in cancer development are missed. Therefore, the hMSC is ideal for the identification of molecular mechanisms regulating telomerase gene expression in stem cells. This study shows that the repression of hTERT expression in hMSC is chromatin based and that modifications of the chromatin environment lead to reactivation of telomerase gene expression. It is shown that repression of ...
Telomerase is a potentially important biomarker and a prognostic indicator of cancer. Several techniques for assessing telomerase activity, including the telomeric repeat amplification protocol (TRAP) and its modified versions, have been developed. Of these methods, real-time quantitative TRAP (RTQ-TRAP) is considered the most promising. In this work, a novel RTQ-TRAP method is developed in which a telomeric repeats-specific molecular beacon is used. The use of the molecular beacon can improve the specificity of the RTQ-TRAP assay, making the method suitable for studying the overall processivity results and the turnover rate of telomerase. In addition, the real-time, closed-tube protocol used obviates the need for post-amplification procedures, reduces the risk of carryover contamination, and supports high throughput. Its performance in synthetic telomerase products and cell extracts suggests that the developed molecular beacon assay can further enhance the clinical utility of telomerase ...
BACKGROUND OBJECTIVE: Recently we found that 20 μg/ml of ginse no side Rh2 (G-Rh2) can inhibit growth,and induce differentiation of hepatocarcino ma cell line SMMC-7721. Re-activation of telomerase may play an important role in carcinogenesis,and cellular immortalization. This study was to explore the m echanism of G-Rh2-induced differentiation of SMMC-7721 cells by detecting tel omerase activity. METHODS: After treated with 20 μg/ml of G-Rh2,telomerase act ivity in SMMC-7721 cells was detected by polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) coupled with enzyme-linked immu ne sorbent assay(ELISA);mRNA levels of human telomerase reverse transcriptase (h TERT),and p21 were measured by reverse transcriptase-polymerase chain reaction (RT-PCR); changes of cell cycle,and expression of Cyclin D1,Cyclin E,P16 protei n were detected by flow cytometry (FCM). RESULTS: G-Rh2 inhibited telomerase ac tivity of SMMC-7721 in a time-dependent manner: the activity decreased
Author Summary The enzyme complex telomerase, with its two main components telomerase reverse transcriptase and telomerase RNA, plays an important role in telomere maintenance. Perturbation of telomere length regulation can ultimately result in cellular senescence (telomere shortening) and is also observed in tumor cells (increased telomere maintenance). Recent studies suggest telomerase RNAs can function independently of the telomerase complex and promote tumor development independently of telomere maintenance. Here we demonstrate that vTR, a herpesvirus-encoded telomerase RNA, serves two distinct functions in MDV-induced tumor formation. vTR has its first function early after infection, when it is part of the telomerase complex and contributes to the survival of rapidly dividing transformed cells. The second function of vTR is independent of telomerase action and essential for formation of solid lymphomas and metastasis. This latter function is likely a consequence of vTR-mediated gene regulation that
Telomerase activity has been regarded as a critical step in cellular immortalization and carcinogenesis and because of this, regulation of telomerase represents an attractive target for anti-tumor specific therapeutics. Recently, one avenue of cancer research focuses on antisense strategy to target the oncogenes or cancer driver genes, in a sequence specific fashion to down-regulate the expression of the target gene. The protein catalytic subunit, human telomerase reverse transcriptase (hTERT) and the template RNA component (hTERC) are essential for telomerase function, thus theoretically, inhibition of telomerase activity can be achieved by interfering with either the gene expression of hTERT or the hTERC of the telomerase enzymatic complex. The present study showed that phosphorothioate antisense oligonucleotide (sASO)-nuclear localization signal (NLS) peptide conjugates targeting hTERC could inhibit telomerase activity very efficiently at 5 μM concentration but less efficiently at 1 μM ...
TY - JOUR. T1 - Low telomerase activity in CD4 + regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation. AU - Kawano, Yutaka. AU - Kim, Haesook T.. AU - Matsuoka, Ken-ichi. AU - Bascug, Gregory. AU - McDonough, Sean. AU - Ho, Vincent T.. AU - Cutler, Corey. AU - Koreth, John. AU - Alyea, Edwin P.. AU - Antin, Joseph H.. AU - Soiffer, Robert J.. AU - Ritz, Jerome. PY - 2011/11/3. Y1 - 2011/11/3. N2 - CD4 +CD25 +Foxp3 + regulatory T cells (Treg) play an important role in the control of chronic graft-versus-host disease (cGVHD). In this study, we examined telomere length and telomerase activity of Treg and conventional CD4 + T cells (Tcon) in 61 patients who survived more than 2 years after allogeneic hematopoietic stem cell transplantation. Cell proliferation and expression of Bcl-2 were also measured in each subset. Treg telomere length was shorter and Treg telomerase activity was increased compared with Tcon (P ,.0001). After transplantation, Treg ...
Telomerase is a ribonucleoprotein which can maintain the length of a chromosome by adding repetitive nucleotide sequences (TTAGGG for vertebrates) to the 3′ end of the chromosome, leading to the endless division of cancer cells.1-5 Telomerase plays a vital role in human cancer, and it has been reported that telomerase is overexpressed in more than 85% of cancer cells. It has been widely recognized as an important biomarker for cancer and a potential therapeutic target.6-8 Currently, polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) and its modified assays are the most popular methods to evaluate telomerase activity in cell extracts and tissues.6,9,10 Although they have excellent sensitivity, the relatively complex detection process and the intrinsic drawbacks of PCR-based assay, including the risk of carry-over contamination and susceptibility to polymerase inhibition by cell extracts, have led to the development of many alternative PCR-free methods, ...
Breast cancer is a heterogeneous disease that includes numerous biological entities with specific pathological characteristics and variable biological behavior. In this study we intended to investigate the presence of telomerase activity in malignant and benign breast lesions. Telomerase is a ribonucleoprotein complex. It contains three subunits: catalytic subunit of human telomerase reverse transcriptase, telomerase RNA subunit and protein subunit. Telomerase activity is present in various biological processes like aging, stem cell diseases and malignant growth. We analyzed telomerase activity in 102 breast carcinomas, 20 fibrocystic lesions, 20 fibroadenomas and 20 samples of normal beast tissue. Results obtained by TRAP assay (telomeric repeat amplification protocol) were correlated with various clinicopathologic parameters: patient age, size and histological grade of tumor, axillary lymph node status, steroid receptors, HER-2 status, Ki-67 analysis and Cathepsin D values. We also analyzed ...
Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase
In this research we investigated the change transcriptase subunit of telomerase in the dimorphic fungus had senescent traits such as for example delayed growth low replicative potential and reduced success that were similar to the traits seen in budding fungus mutants. recommended that Trt1 is essential for teliospore development in homozygous disrupted diploids which telomerase is normally haploinsufficient in heterozygous diploids. Additionally terminal limitation fragment evaluation in the progeny hinted at choice survival mechanisms comparable to those of budding fungus. BMS 599626 Introduction Telomerase is normally a specific ribonucleic protein complicated that synthesizes the recurring G-rich-DNA motifs constituting telomeres generally in most eukaryotic cells. The central enzyme elements will be the telomerase slow transcriptase (TERT) proteins subunit which really is a BMS 599626 specific slow transcriptase as well as the RNA template for telomere DNA synthesis (TR); both these ...
Telomerase is a ribonucleoprotein complex that elongates telomeres by adding hexameric (TTAGGG) repeats to the telomeric ends of the chromosomes, thus compensating for the continued erosion of telomeres. Telomerase activity is present in unicellular organisms and germ cells, both places where it is expected to play a role in indefinite cycling and protection from shortening of the telomeres. One phenotypic manifestation that is virtually pathognomonic of several cancer cells is the telomerase activity. Telomerase activity is enhanced in several cell types after treatment with ionizing radiation (IR). Whether there is a direct correlation between the levels of telomerase activity and IR response for tumor cell kill is yet to be addressed in detail. In this review, information is summarized on telomerase activity as a measure for monitoring the radiocurability of tumors. As tumor growth is partly due to deregulated cell cycling, insights into telomerase activity through the cell cycle may prove ...
Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in
Understanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2-8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved
Cellular senescence is defined by the limited proliferative capacity of normal cultured cells. Immortal cells overcome this regulation and proliferate indefinitively. One step in the immortalization process may be reactivation of telomerase activity, a ribonucleoprotein complex, which, by de novo synthesized telomeric TTAGGG repeats, can prevent shortening of the telomeres. Here we show that immortal human skin keratinocytes, irrespective of whether they were immortalized by simian virus 40, human papillomavirus 16, or spontaneously, as well as cell lines established from human skin squamous cell carcinomas exhibit telomerase activity. Unexpectedly, four of nine samples of intact human skin also were telomerase positive. By dissecting the skin we could show that the dermis and cultured dermal fibroblasts were telomerase negative. The epidermis and cultured skin keratinocytes, however, reproducibly exhibited enzyme activity. By separating different cell layers of the epidermis this telomerase ...
TY - JOUR. T1 - Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements. AU - Casillas, Mark. AU - Brotherton, Scott L.. AU - Andrews, Lucy G.. AU - Ruppert, J. Michael. AU - Tollefsbol, Trygve O.. PY - 2003/10/16. Y1 - 2003/10/16. N2 - Elucidation of the mechanisms governing expression of the human telomerase reverse transcriptase (hTERT) is important for understanding cancer pathogenesis. Approximately 90% of tumors express hTERT, the major catalytic component of telomerase. Activation of telomerase is an early event, and high levels of this activity correlate with poor prognosis. Recent studies have shown that the transcription factors c-Myc and Mad1 activate and repress hTERT, respectively. It is not clear how these transcription factors compete for the same recognition sequence in the hTERT core promoter region. Studies have shown that the combined expression of SV40 large T antigen (T-Ag), hTERT, and H-Ras is able to transform ...
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109718 - comparing darunavir/ritonavir monotherapy versus darunavir/ritonavir and 2 N(t)RTIs for maintenance of virological suppression, there were not significant differences between 2 arms after 3 years of follow-up in telomerase activity or mean change per year of telomere length. [Patients in the sub-study had a mean age of 44 years and had received NRTI for a mean of 6.4 years (range 1-20 years). As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026). There was no significant association between TL and either the duration of prior NRTI treatment (p = 0.894) or the use of a PI versus NNRTI (p = 0.107). There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively).....Factors associated with baseline TL and telomerase activity were analysed by multivariable ...
Telomeres, the natural ends of linear eukaryotic chromosomes, are essential for chromosome stability. Because of the nature of DNA replication, telomeres require a specialized mechanism to ensure their complete duplication. Telomeres are also capable of silencing the transcription of genes that are located near them. In order to identify genes in the budding yeast Saccharomyces cerevisiae that are important for telomere function, a screen was conducted for genes that, when expressed in high amounts, would suppress telomeric silencing. This screen lead to the identification of the gene TLC1 (telomerase component 1). TLC1 encodes the template RNA of telomerase, a ribonucleoprotein required for telomere replication in a variety of organisms. The discovery of TLC1 confirms the existence of telomerase in S. cerevisiae and may facilitate both the analysis of this enzyme and an understanding of telomere structure and function. ...
Our lab is interested in telomere function, the regulation of telomere length and the biochemistry of telomerase. Telomeres are essential for both chromosome stability and for length maintenance. Telomerase is a ribonucleoprotein reverse transcriptase that synthesizes telomere repeats onto chromosome ends. Telomerase is required for telomerase length maintenance: in the absence of telomerase, telomeres shorten progressively. To understand the telomerase, we initially focused on the well characterized Tetrahymena enzyme. We extensively characterized the functional regions of the Tetrahymena telomerase RNA. Using a reconstitution system, we mapped the essential RNA functional region. To extend this analysis to mammalian telomerase we established the secondary structure of the vertebrate telomerase RNA. We cloned and sequenced telomerase RNA genes from 35 vertebrate species and determined the secondary structure using phylogenetic comparative analysis. We identified four highly conserved domains in ...
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5-TTAGGG-3. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt
The foundational understanding of the role of telomeres and telomerase in disease has been rooted in curiosity-driven science, in simple systems and model organisms (22). One major theme that emerges at the intersection between this fundamental science and disease genetics is that relatively small, subtle changes affecting telomerase abundance or function can influence telomere length and, in turn, disease risk (23). The exquisite sensitivity of telomere length to these small changes is related to the fact that telomerase is in very low abundance and its activity is tightly regulated. In yeast, mice, and humans, the number of telomere ends exceeds the number of telomerase molecules (refs. 24, 25, and reviewed in refs. 23, 26). The low levels of telomerase set up a system wherein not all telomeres are elongated during a given cell cycle even when telomerase is normally expressed (27). There are at least three additional limits on telomerase activity. The first is that the essential telomerase ...
Telomerase is an RNA-dependent DNA polymerase that uses an RNA component to add telomeric repeat sequences at the ends of chromosomes. Besides the RNA component which serves as the template that specifies the telomeric repeat, the telomerase complex contains a reverse transcriptase protein (TRT) and various accessory proteins including the telomerase-associated protein 1 (TP1). Telomerase activity is low in most somatic cells, causing the gradual shortening of telomeres which can ultimately lead to telomere fusion and cell death. High levels of telomerase activity are widely seen in cancerous cells and while recent experiments have suggested that telomerase may be a viable target in cancer therapy, expression levels of TP1 do not correlate with malignancy. At least two isoforms of TP1 are known to exist ...
While telomerase (hTERT) activity is absent from normal somatic cells, reactivation of hTERT expression is a hallmark of cancer cells. Telomerase activity is is required for avoiding replicative senescence and supports immortalization of cellular proliferation. Only a minority of cancer cells rely on a telomerase-independent process known as alternative lengthening of telomeres, ALT, to sustain cancer cell proliferation. Multiple genetic, epigenetic, and viral mechanisms have been found to deregulate telomerase gene expression increasing the risk of cellular transformation. Here, we review the different strategies used by the Human T cell leukemia virus type 1, HTLV-I, to activate hTERT expression and stimulate its enzymatic activity in virally-infected CD4 T cells. The implications of hTERT reactivation in HTLV-I pathogenesis and disease treatment are discussed.
In most eukaryotes, the progressive loss of chromosome-terminal DNA sequences is counteracted by the enzyme telomerase, a reverse transcriptase that uses part of an RNA subunit as template to synthesize telomeric repeats. Many cancer cells express high telomerase activity, and mutations in telomeras …
This is a request for an REU supplement to the PIs CAREER AWARD project Molecular Evolution of Telomerase Ribonucleoprotein: A Phylogenetic Study of Telomerase RNA Structure and Function (06/15/2007 06/14/2012). To integrate research and undergraduate education, this proposed work for the REU supplement will include two objectives: (1) To update and improve the web-based Telomerase Database that we established in 2007; (2) to give undergraduate students interdisciplinary training in bioinformatics and molecular biology. Two talented undergraduate students, Ryan Niedzielko and Anthony Young, have been recruited to carry out this project for the summer of 2009. They are selected because of their outstanding academic performance. Ryan Niedzielko has a GPA of 3.92 and Anthony Young has a GPA of 3.41. Ryan and Anthony will work together to complete the proposed project. They will search and read literatures to identify new telomerase-related protein and RNA genes. They will learn how to use ...
Purpose: : We had previously shown that ultraviolet irradiation (UVR) significantly and maximally increases telomerase activity in canine lens epithelial cells at a dose of 600 J/m2 followed by a recovery period of 8 hours. However, we had not evaluated telomerase gene transcription. Therefore, we hypothesized that an acute dose of UVR followed by an 8 hour recovery period would up-regulate TERT, the catalytic subunit of telomerase, and possibly up-regulate TR, the RNA component of telomerase. Methods: : Six freshly harvested normal adult canine lenses per group were exposed to 0 or 600 J/m2 UVR, then allowed to recover for 8 or 24 hours prior to RNA extraction. Quantitative RT-PCR was performed using primers for canine TERT and TR, designed in our laboratory. A greater than two-fold difference was deemed physiologically relevant. Data is expressed as fold-difference and HPRT was used as the housekeeping gene. Results: : Lenses exposed to UVR, then recovered for 8 hours had a 9.88 fold ...
In almost all eukaryotes, the task of solving the end-replication problem and counteracting telomere erosion is assigned to the telomerase enzyme complex (Greider and Blackburn, 1985). The active telomerase holoenzyme in mammalian cells exists as a dimer and consists of the telomerase reverse transcriptase (TERT), the telomerase RNA component (TERC) and dyskerin (Cohen et al., 2007). In humans, telomerase is expressed during the early stages of embryogenesis, and its expression is subsequently repressed in most somatic cells, except the male germ line, activated lymphocytes and stem cells found in certain regenerative tissues (Wright et al., 1996). Furthermore, the vast majority of human cancer cells reactivate telomerase, and are thus capable of proliferating indefinitely (Kim et al., 1994). Regulation of telomerase is primarily exerted at the level of TERT transcription. Extensive analysis of the promoter region has uncovered many transcriptional binding sites and regulatory elements, ...
Wounds within the oral mucosa, similarly to fetal wounds, exhibit rapid healing with reduced scarring. We hypothesized that a progenitor population resident within the oral mucosal lamina propria (OMLP) contributes to this preferential healing. Progenitor cells (PC) were reliably isolated from the OMLP by differential adhesion to fibronectin. Isolated colonies originating from a single cell demonstrated a rapid initial phase of proliferation, completing in excess of 50 population doublings (PDs) before entering cellular senescence. These data were supported by the expression of active telomerase within both developing colonies and expanded clones as assessed by immunocytochemistry (ICC) and the quantitative telomeric repeat amplification protocol. FACS analysis confirmed expression of the stem cell markers CD44, CD90, CD105, and CD166, but negative expression of CD34 and CD45 ruling out a hematopoietic or fibrocyte origin for these progenitors. A neural crest origin was confirmed by increased ...
This postdoctoral study investigated the effects of the green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), on telomerase gene expression in MCF-7 breast cancer cells and human teratocarcinoma cells to determine if the down regulation of this gene is the mechanism by which EGCG induces apoptosis of cancer cells. ...
Telomere shortness in human beings is a prognostic marker of ageing, disease, and premature morbidity. We previously found an association between 3 months of comprehensive lifestyle changes and increased telomerase activity in human immune-system cells. We followed up participants to investigate long-term effects.
Our studies using systemic ribozyme-based targeting of TER suggest a direct link between the functional activity of the telomerase complex and the metastatic progression of B16-F10 melanoma in tumor-bearing C57Bl/6 mice. That cationic liposome:DNA complex-based ribozyme targeting was able to produce significant antitumor effects in a mouse tumor model system is of significance because of the potential challenges inherent in using such a model. Laboratory mouse strains, such as the one used here, have very long telomeres and high telomerase activity in many of its normal tissues (26) . Thus, systemic targeting of telomerase in this system might have been expected to produce either widespread toxicity (if successful in every organ), or no effects given the time frame over which the level of telomerase complex was reduced.. The lack of antitumor activity of the disabled mutant anti-TER 180 ribozyme strongly suggests that the in vivo mechanism of ribozyme action is TER cleavage. We note that ...
Telomerase activity has been demonstrated in normal tissues from renewal organs such as skin, small intestine, and the lymphoproliferative system. Renewal organs must maintain the ability to proliferate in response to certain stimuli over the lifetime of an individual. Like skin, the oesophageal epithelium is normally in a state of slow renewal and has the capacity for accelerated cell proliferation in response to injury. Our finding that trace telomerase activity is present in biopsies of endoscopically normal oesophagus is consistent with the concept that the oesophagus is a renewal organ. We have previously demonstrated that expression of telomerase RNA (hTR) localises to the basal proliferative cells of the oesophageal squamous epithelium.40 Although cells from the oesophagus and other renewal organs normally express low levels of telomerase, studies in the small intestine and in CD34+ stem cells have demonstrated that such telomerase expression can only attenuate, but not prevent, telomere ...
Maintenance of telomere length is critical for continued growth and survival of tumor cells, and telomerase activation maintains telomeres in proliferating tumor cells. In this study, we observed a high level of telomerase activity in all myeloma cell lines tested, versus low-level telomerase activity in normal diploid fibroblasts and normal plasma cells. There was an inverse correlation (r = rs = −0.8) between telomere length and telomerase activity among myeloma cell lines, as previously reported in B-cell chronic lymphocytic leukemia (25). These findings are also consistent with observations in non-hematopoietic cancers such as hepatocellular carcinoma (26), breast cancer (27), and prostate cancer (28), in which shortened telomeres are associated with elevated telomerase activity. In our study, telomeres were shorter in myeloma than in normal plasma cells, suggesting that telomerase directed therapy may induce crisis after fewer cell divisions.. In the present study, we assessed telomerase ...
Certain non-nucleoside compounds that will selectively inhibit telomerase by targeting the nucleic add structures, such as G-quadruplexes, that may be associated with human telomeres or telomerase have been identified. Inhibition of human telomerase by two perylenetetracarboxylic acid diimides and a carbocyanine has been demonstrated. 1H-NMR studies have evidenced the stabilization of a G-quadruplex by the perylenetetracarboxylic acid diimide compounds and provided evidence that these and structurally related compounds inhibit the telomerase enzyme by a mechanism consistent with interaction with G-quadruplex structures.
Link to Pubmed [PMID] - 27503890. Proc. Natl. Acad. Sci. U.S.A. 2016 Aug;113(34):E5024-33. Oncogene-induced senescence (OIS) is a critical tumor-suppressing mechanism that restrains cancer progression at premalignant stages, in part by causing telomere dysfunction. Currently it is unknown whether this proliferative arrest presents a stable and therefore irreversible barrier to cancer progression. Here we demonstrate that cells frequently escape OIS induced by oncogenic H-Ras and B-Raf, after a prolonged period in the senescence arrested state. Cells that had escaped senescence displayed high oncogene expression levels, retained functional DNA damage responses, and acquired chromatin changes that promoted c-Myc-dependent expression of the human telomerase reverse transcriptase gene (hTERT). Telomerase was able to resolve existing telomeric DNA damage response foci and suppressed formation of new ones that were generated as a consequence of DNA replication stress and oncogenic signals. Inhibition ...
The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
TY - JOUR. T1 - The conserved structure of plant telomerase RNA provides the missing link for an evolutionary pathway from ciliates to humans. AU - Song, Jiarui. AU - Logeswaran, Dhenugen. AU - Castillo-González, Claudia. AU - Li, Yang. AU - Bose, Sreyashree. AU - Aklilu, Behailu Birhanu. AU - Ma, Zeyang. AU - Polkhovskiy, Alexander. AU - Chen, Julian J.L.. AU - Shippen, Dorothy E.. PY - 2019/12/3. Y1 - 2019/12/3. N2 - Telomerase is essential for maintaining telomere integrity. Although telomerase function is widely conserved, the integral telomerase RNA (TR) that provides a template for telomeric DNA synthesis has diverged dramatically. Nevertheless, TR molecules retain 2 highly conserved structural domains critical for catalysis: a template-proximal pseudoknot (PK) structure and a downstream stem-loop structure. Here we introduce the authentic TR from the plant Arabidopsis thaliana, called AtTR, identified through next-generation sequencing of RNAs copurifying with Arabidopsis TERT. This RNA ...
Telomerase[edit]. The HeLa cell line was derived for use in cancer research. These cells proliferate abnormally rapidly, even ... Like many other cancer cells,[36] HeLa cells have an active version of telomerase during cell division,[37] which prevents the ... Ivanković M, Cukusić A, Gotić I, Skrobot N, Matijasić M, Polancec D, Rubelj I (2007). "Telomerase activity in HeLa cervical ...
Telomerase[edit]. Cancer cells have unique features that make them "immortal" according to some researchers. The enzyme ... While the telomeres of most cells shorten after each division, eventually causing the cell to die, telomerase extends the ... telomerase is used to extend the cancer cell's life span. ...
... fold named TEL patch that interacts with the catalytic subunit of telomerase, hTERT, has been proven essential for telomerase ... Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M (2007). "The POT1-TPP1 telomere complex is a telomerase ... Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M (2007). "The POT1-TPP1 telomere complex is a telomerase ... TPP1 has also been demonstrated as the only pathway required for recruitment of telomerase to chromosome ends, and it also ...
Retrotransposons also spread by copying DNA and RNA from one another, and telomerase contains an RNA that is used as template ... Podlevsky JD, Bley CJ, Omana RV, Qi X, Chen JJ (January 2008). "The telomerase database". Nucleic Acids Research. 36 (Database ...
This event can be counteracted by telomerase, an enzyme that extends the ends of the chromosomes by copying the telomeres and ... Chan SR, Blackburn EH (2004). "Telomeres and telomerase". Philos. Trans. R. Soc. Lond. B Biol. Sci. 359 (1441): 109-21. doi: ...
Low telomerase activity. Accumulate into damaged tissue by intravenous or local injections. Replenish new functional cells ... Hela cells and human fibroblast-derived iPS cells showed high telomerase activity while Muse was at nearly the same level as ... This can be explained in part by their intrinsically low telomerase activity, eradicating the risk of tumorigenesis through ... Muse cells are characterized by low telomerase activity, not a strong indicator of tumorigenicity. ...
Telomerase gene therapy utilizing an adeno-associated virus at the Spanish National Cancer Research Centre (CNIO), has ... "Telomeres and Telomerase Group". Spanish National Cancer Research Centre. 19 May 2008. Archived from the original on 3 December ... "Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer". EMBO Molecular ... BioViva's research interests are based on preclinical research of both the enzyme telomerase and inhibition of myostatin. ...
"Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies". Genome Medicine. 8 (1): 69. doi: ... Such phenomena is brought about by the presence of telomerase, which would catalyse the reaction of adding nucleotide sequences ... It replenishes the telomeres that are lost during DNA replication, compensating for enough telomerase sequence so that the ... Studies have discovered the linkage between the abnormal replenishing of telomere, overactivity of telomerase, and cancer ...
"Nucleolin interacts with telomerase". The Journal of Biological Chemistry. 279 (49): 51508-15. doi:10.1074/jbc.M407643200. PMID ... and Telomerase reverse transcriptase. GRCh38: Ensembl release 89: ENSG00000115053 - Ensembl, May 2017 GRCm38: Ensembl release ...
Then, after the mice had prematurely aged, they restored telomerase activity by reactivating the telomerase gene. As a result, ... However, activating telomerase in humans could potentially encourage the growth of tumours. Most known genetic interventions in ... However, telomere length in wild mouse strains is unrelated to lifespan, and mice lacking the enzyme telomerase do not have a ... Callaway E (2010). "Telomerase reverses ageing process". Nature. doi:10.1038/news.2010.635. Blagosklonny MV (March 2009). " ...
Geron has granted a license to Telomerase Activation Sciences to sell TA-65, the telomerase activator agent also derived from ... Geron's progress with telomerase vaccines attracted a modest monetary investment in 2005 from Merck. GRN1005, an LRP-directed ... Geron originally investigated telomerase as a means of understanding and modifying human aging. However, Geron has ceased aging ... The company is in the early stages of developing a telomerase based treatment for HIV called TAT0002, which is the saponin ...
... s use telomerase, a protein that restores telomeres, to protect their DNA and extend their cell division limit (the ... Cong YS, Wright WE, Shay JW (September 2002). "Human telomerase and its regulation". Microbiology and Molecular Biology Reviews ...
Telomerase is expressed by most vertebrates during embryonic stages, but is generally absent from adult stages of life. However ... Telomerase is especially present in 'Green Spotted' lobsters - whose markings are thought to be produced by the enzyme ... This longevity may be due to telomerase, an enzyme that repairs long repetitive sections of DNA sequences at the ends of ... Cong YS, Wright WE, Shay JW (September 1, 2002). "Human Telomerase and Its Regulation". Microbiology and Molecular Biology ...
Studies have shown that 90 percent of cancer cells contain large amounts of an enzyme called telomerase. Telomerase is an ... This is because they contain raised amounts of telomerase. The idea that the human body can be repaired in old age to a more ... A cancer cell has in essence turned on the telomerase gene, and this allows them to have an unlimited amount of divisions ... Peter J. Hornsby (2007). "Telomerase and the aging process". Experimental Gerontology. 42 (7): 575-81. doi:10.1016/j.exger. ...
Jiang, J; Wang, Y; Sušac, L; Chan, H; Basu, R; Zhou, ZH; Feigon, J (17 May 2018). "Structure of Telomerase with Telomeric DNA ... Zhang, Q; Kim, NK; Feigon, J (20 December 2011). "Architecture of human telomerase RNA". Proceedings of the National Academy of ... Theimer, CA; Blois, CA; Feigon, J (4 March 2005). "Structure of the human telomerase RNA pseudoknot reveals conserved tertiary ... Her research group has invested significant effort in determining the structure of telomerase, using NMR, X-ray crystallography ...
Telomerase is expressed by most vertebrates during embryonic stages but is generally absent from adult stages of life. However ... Homeostatic telomerase activity observed in both asexual and sexual animals is not sufficient to maintain telomere length, ... The term "immortalization" was first applied to cancer cells that expressed the telomere-lengthening enzyme telomerase, and ... Cong YS (2002). "Human Telomerase and Its Regulation". Microbiology and Molecular Biology Reviews. 66 (3): 407-425. doi:10.1128 ...
Telomerase "replenishes" the telomere "cap." In most multicellular eukaryotic organisms, telomerase is active only in germ ... The cloning of the catalytic component of telomerase enabled experiments to test whether the expression of telomerase at levels ... January 2011). "Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice". Nature. 469 (7328): ... Telomeres and Telomerase: The Means to the End Nobel Lecture by Elizabeth Blackburn, which includes a reference to the impact ...
Small nuclear ribonucleoprotein-associated protein N is a protein that in humans is encoded by the SNRPN gene.[4][5] The protein encoded by this gene is one polypeptide of a small nuclear ribonucleoprotein complex and belongs to the snRNP SMB/SMN family. The protein plays a role in pre-mRNA processing, possibly tissue-specific alternative splicing events. Although individual snRNPs are believed to recognize specific nucleic acid sequences through RNA-RNA base pairing, the specific role of this family member is unknown. The protein arises from a bicistronic transcript that also encodes a protein identified as the SNRPN upstream reading frame (SNURF). Multiple transcription initiation sites have been identified and extensive alternative splicing occurs in the 5' untranslated region. Additional splice variants have been described but sequences for the complete transcripts have not been determined. The 5' UTR of this gene has been identified as an imprinting center. Alternative splicing or deletion ...
Telomerase. RNA nucleotidyltransferase. Template-directed. RNA polymerase I. II. III. IV. V. ssRNAP POLRMT. Primase 1. 2. ...
Telomerase. DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase. RNA nucleotidyltransferase. RNA polymerase/DNA ...
Telomerase. RNA nucleotidyltransferase. Template-directed. RNA polymerase I. II. III. IV. V. ssRNAP POLRMT. Primase 1. 2. ...
Telomerase. DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase. RNA nucleotidyltransferase. RNA polymerase/DNA ...
Telomerase. DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase. RNA nucleotidyltransferase. RNA polymerase/DNA ...
Telomerase. RNA nucleotidyltransferase. Template-directed. RNA polymerase I. II. III. IV. V. ssRNAP POLRMT. Primase 1. 2. ...
Telomerase. DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase. RNA nucleotidyltransferase. RNA polymerase/DNA ...
In their telomerase research, West and colleagues at Geron cloned the RNA component of telomerase and collaborated with Thomas ... Michael D. West is a biogerontologist, and a pioneer in stem cells, cellular aging and telomerase. He is the founder and CEO of ... Geron published evidence of the role of telomerase in cancer and cell immortalization in collaboration with Woodring Wright and ... "The RNA Component of Human Telomerase". Science. 269: 1236-1241. doi:10.1126/science.7544491. PMID 7544491.CS1 maint: multiple ...
... telomerase activity, and advanced clinical grade. Transl On- col. 2012; 5: 56-65. Armanios M. Telomerase and idiopathic ... thus promoting telomerase-mediated elongation. The true nature of TERRA's interaction with telomerase remains incompletely ... At the same time, telomerase activity is known to be at its greatest when telomeres are short and at its lowest activity when ... Ng L. J., Cropley J. E., Pickett H. A., Reddel R. R., Suter C. M. (2009). Telomerase activity is associated with an increase in ...
These include Telomerase, P53, and HINT1. Telomerase is a protein complex with telomerase reverse transcriptase (TERT), an RNA ... and both reptin and pontin have been shown to be key factors in telomerase assembly and activity. Telomerase is an important ... "Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly". Cell. 132 (6): 945-957 ...
"Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies". Genome Medicine. 8 (1): 69. doi: ... This occurs through telomerase activation or the activation of a telomere-recombination pathway (i.e., the ALT pathway). Thus, ... For example, the telomerase inhibitor imetelstat, first proposed in 2003, has been held up in clinical trials due to ... Although telomerase activation does not occur during the cell cycle of normal somatic human cells, the association between ...
Lustig AJ (1999). "Crisis intervention: The role of telomerase". Proc Natl Acad Sci USA. 96 (7): 3339-41. Bibcode:1999PNAS... ...
We had no idea when we started this work that telomerase would be involved in cancer, but were simply curious about how ... Working with Blackburn, Greider helped in 1989 to identify the RNA-based telomerase-the enzyme that creates the crucial ... From an evolutionary standpoint, for example, the similarities between telomerase and the reverse transcriptase in retroviruses ... and telomerase, the enzyme that assists in this process, findings that are important in the study of cancer, aging and stem ...
Telomeres and Telomerase: Methods and Protocols, Second Edition builds upon the telomerase assays featured in the popular first ... Authoritative and practical, Telomeres and Telomerase: Methods and Protocols, Second Edition serves as an ideal, up-to-date ... Visualization of Human Telomerase Localization by Fluorescence Microscopy Techniques Eladio Abreu, Rebecca M. Terns, Michael P ... Telomere Terminal G/C Strand Synthesis: Measuring Telomerase Action and C-Rich Fill-In ...
Cell-tracing analysis reveals that a disperse group of cells in the mouse liver express the enzyme telomerase, which preserves ... Telomerase defects are associated with tissue scarring (fibrosis) in the livers of both mice and humans4,5, but which cells in ... The telomerase enzyme and liver renewal. Cell-tracing analysis reveals that a disperse group of cells in the mouse liver ... However, elevated telomerase levels are seen in various animal and human stem cells that must retain their replicative capacity ...
... Bev A. Kupf bevakupf at ebv.mimnet.northwestern.edu Tue Jul 22 08:38:31 EST 2003 *Previous message: Telomerase ...
... telomerase inhibition itself is not sufficient. Thus, an effective telomerase inhibitor would be expected to shorten telomeres ... but did not inhibit telomerase activity in cells from healthy donors that had been treated with cytokines to ramp up telomerase ... The investigational telomerase inhibitor imetelstat (Geron) shows significant activity against two chronic myeloproliferative ... Cite this: Telomerase Inhibitor Imetelstat Reverses Marrow Fibrosis - Medscape - Sep 03, 2015. ...
2000) Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse ... telomerase reverse transcriptase. Telomerase is a large, multisubunit ribonucleoprotein (RNP) that replicates the 3′ end of ... 2007) Human telomerase RNA accumulation in Cajal bodies facilitates telomerase recruitment to telomeres and telomere elongation ... The telomerase holoenzyme includes a unique reverse transcriptase [telomerase reverse transcriptase (TERT)], an essential RNA ( ...
... telomerase activity Human telomerase reverse transcriptase (TERT) gene on genecards.org The Telomerase Database - A Web-based ... Telomerase is a good biomarker for cancer detection because most human cancers cells express high levels of it. Telomerase ... Telomerase activation has been observed in ~90% of all human tumors, suggesting that the immortality conferred by telomerase ... Telomerase reverses telomere shortening. Telomerase restores short bits of DNA known as telomeres, which are otherwise ...
It associates with telomerase and, during its interaction with CDC13, telomerase activity is promoted [PMID: 12169735, PMID: ... Telomerase activating protein Est1 (IPR019458). Short name: EST1 Overlapping homologous superfamilies *Tetratricopeptide-like ... The Est1 subunit of Saccharomyces cerevisiae telomerase makes multiple contributions to telomere length maintenance.. Genetics ... Est1p as a cell cycle-regulated activator of telomere-bound telomerase.. Science 297 1023-6 2002 ...
Actions of human telomerase beyond telomeres.. Cong Y1, Shay JW.. Author information. 1. Key laboratory for Cell Proliferation ... Telomerase has fundamental roles in bypassing cellular aging and in cancer progression by maintaining telomere homeostasis and ... This review will provide an update on the extracurricular activities of telomerase in apoptosis, DNA repair, stem cell function ... However, recent studies have led some investigators to suggest novel biochemical properties of telomerase in several essential ...
Telomerase. Gliederung. 1. Telomere. 2. Telomerase. 3. Krebs 4. Krebstherapie möglich?. 5. Fazit Telomerase. 6. Quellen. 1.1 ... Transcript of Telomerase -. 1.Telomere. 2.Telomerase. 2.1 Entdeckung. 2.2 Struktur. 2.3 Vorkommen. 2.4 Regulation. 2.5 Aufgabe ... Immunsystemzellen und Keimzellen können sich durch die Telomerase ständig erneuern. Negative Aspekte:. Telomerase kann zu der ... Telomerase ist ein Enzym. stellt die Telomere wieder her macht Zellteilung mit einer geringen Anzahl an Telomeren möglich 2.1 ...
Author Summary Telomerase mutations in humans give rise to premature ageing syndromes. In animals, the wealth of knowledge in ...
Tag: telomerase. Clinical TrialsEthicsMedical Ethics. Would you pay $1 million to enroll in a phase 1 clinical trial of an " ... Libella Gene Therapeutics, LLC made the news last week for announcing a "pay-to-play" trial of its telomerase-based anti-aging ...
The ribonucleoprotein enzyme telomerase synthesizes telomeric DNA by copying an internal RNA template sequence. The telomerase ... The S. cerevisiae activity required the telomerase RNA gene TLC1 but not the EST1 gene, both of which are required for normal ... An inherently high stalling frequency of the S. cerevisiae telomerase may account for its in vitro properties and for the ...
Telomerase RNA component, also known as TR, TER or TERC, is an ncRNA found in eukaryotes that is a component of telomerase, the ... "Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase ... Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mice suggest that telomerase ... Chang JT, Chen YL, Yang HT, Chen CY, Cheng AJ (July 2002). "Differential regulation of telomerase activity by six telomerase ...
2008) How telomerase reaches its end: Mechanism of telomerase regulation by the telomeric complex. Mol Cell 31:153-165. ... Beyond the recurring questions concerning the telomerase-retrotransposon relationship, unusual aspects of telomerase and ... telomerase RNA) and DKC1 (dyskerin, an RNA-binding telomerase subunit) mutations in some patients (57). This conclusion was ... Schematic of telomerase. Telomerase RNA (TER, green) with its pseudoknot structure has the template region base-paired to ...
... including telomerase and complexes that regulate transcription. Their research also focuses on the telomeric DNA-protein ... complexes that cap the ends of human chromosomes and help regulate telomerase. The overarching goal is to understand the ... telomerase). In addition, telomerase is biologically and medically important; telomerase mutations lead to diseases involving ... Telomerase, an RNP enzyme critical for chromosome end replication, provides the subject for much of our research. Telomerase is ...
Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide- ... Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signalling and associated ... Here it is shown that reactivation of endogenous telomerase activity in mice extends telomeres, reduces DNA damage signalling, ... To this end, we engineered a knock-in allele encoding a 4-hydroxytamoxifen (4-OHT)-inducible telomerase reverse transcriptase- ...
In tumor-derived cell lines telomeres are maintained by the ribonucleoprotein enzyme telomerase. Telomerase activity is ... In tumor-derived cell lines telomeres are maintained by the ribonucleoprotein enzyme telomerase. Telomerase activity is ... Telomerase activity in human cancer Curr Opin Oncol. 1996 Jan;8(1):66-71. doi: 10.1097/00001622-199601000-00012. ... This continuing telomere erosion ultimately leads to the activation of telomerase, a necessary event for the sustained growth ...
For the first time ever a natural compound has been discovered that activates the enzyme telomerase in the human body. The ... Telomerase Anti-Aging. The enzyme telomerase replenishes telomeres. Telomerase activation in the human body is a requirement ... Telomerase Enzymes Stop Telomeres From Shrinking. It has been proven that the enzyme telomerase can halt the shrinking of ... Telomerase does not stop cancer. Quite the opposite, the research is coming up with ways to inhibit telomerase expression in ...
Telomeres and Telomerase RT2 Profiler PCR Array The Rat Telomeres & Telomerase RT² Profiler PCR Array profiles the expression ... Telomeres and Telomerase RT2 Profiler PCR Array The Human Telomeres & Telomerase RT² Profiler PCR Array profiles the expression ... Telomeres and Telomerase RT2 Profiler PCR Array The Mouse Telomeres & Telomerase RT² Profiler PCR Array profiles the expression ... Telomerase (TERT), a reverse transcriptase, forms a complex with an RNA template and cofactors to extend telomeres. The ...
Telomerase ribonucleoprotein complex - RNA-binding domain (IPR021891). Short name: Telomerase_RBD Overlapping homologous ... The reverse transcriptase component of the Tetrahymena telomerase ribonucleoprotein complex.. Proc. Natl. Acad. Sci. U.S.A. 95 ... The reverse transcriptase component of the Tetrahymena telomerase ribonucleoprotein complex.. Proc. Natl. Acad. Sci. U.S.A. 95 ... The reverse transcriptase component of the Tetrahymena telomerase ribonucleoprotein complex.. Proc. Natl. Acad. Sci. U.S.A. 95 ...
In tumors and germ cells telomerase is quite active, but otherwise dormant. Can telomerase stop aging? ... Telomerase is a protein thats found in all cells. ... Telomerase is a protein thats found in all cells, but in ... Second, researchers have figured out how to extract telomerase and synthesize it. Potentially, if active telomerase is added to ... Telomerase has the aging research community excited for two reasons. First, since its naturally active in tumors and can be ...
Telomerase activity in small-cell and non-small-cell lung cancers. J Natl Cancer Inst 1995;87:895-902.CrossRefPubMedGoogle ... Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer 1997;33:787-91.CrossRefPubMedGoogle Scholar ... Correlating telomerase activity levels with human neuroblastoma outcomes. Nat Med 1995;1:249-55.CrossRefPubMedGoogle Scholar ... concomitant with activation of telomerase. Telomerase is activated in around 80% of human cancers but not in usual somatic ...
... Aubrey de Grey ag24 at mole.bio.cam.ac.uk Thu Jun 15 09:55:29 EST 2000 *Previous ...
Gene Ontology Term: telomerase inhibitor activity. GO ID. GO:0010521 Aspect. Molecular Function. Description. Binds to and ... stops, prevents or reduces the activity of telomerase.. View GO Annotations in other species in AmiGO ...
Telomerase activity is a useful cancer-cell detecting marker in some t … ... Telomerase, a critical enzyme responsible for continuous cell growth, is repressed in most somatic cells except proliferating ... Telomerase activity is a useful cancer-cell detecting marker in some types of cancers in which almost all cases show telomerase ... Telomerase as tumor marker Cancer Lett. 2003 May 15;194(2):221-33. doi: 10.1016/s0304-3835(02)00709-7. ...
In cancer cells, telomerase helps maintain the length of caps on the ends of chromosomes called telomeres. This helps cancer ... Blocking telomerase increases cancer cells sensitivity to radiation treatment. *Download PDF Copy ... In normal cells lacking the telomerase enzyme, telomeres get shorter each time cells divide. They continue doing so until ... Before treating cells with ionizing radiation, the researchers blocked an enzyme called telomerase, found in over 90 percent of ...
Telomere and Telomerase. The safety and scientific validity of this study is the responsibility of the study sponsor and ...
... telomerase activity is associated with the telomerase RNA hTR [13], the telomerase RNA-binding protein TP1/TLP1 [5,12] and the ... Recognition of telomerase RNA by TP2 was species specific, and nucleotides 10-159 of hTR were sufficient for telomerase ... Reconstitution of human telomerase activity in vitro.. Beattie TL1, Zhou W, Robinson MO, Harrington L. ... Telomerase is a ribonucleoprotein enzyme complex that adds single-stranded telomere DNA to chromosome ends [1]. The RNA ...
Telomerase plays a key role in maintaining the length of telomere by adding G-rich repeat sequences. Its activity has been ... Telomerase, the ribonucleoprotein complex, and its accessory proteins are required to maintain the telomere sequence. ... Almost 85% of tumor cells compensate for telomere loss aided by telomerase-associated protein complex and shelter in complex or ... This review presents the molecular view of the telomere and telomerase along with its associated complex structures. It also ...

No FAQ available that match "telomerase"