Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis of telomeric DNA using intrinsic RNA as a template. The enzyme was originally found in a ciliate Tetrahymena, and has been extensively investigated using ciliates or budding yeast. In mammals, the enzyme is highly active in most cancer cells and germ cells, but is inactive in most somatic cells, suggesting the activation of telomerase may be important for the continued cell growth or progression of cancer cells. Recently, two protein components of the mammalian telomerase have been identified using homology to the sequencing data from unicellular eukaryotes. Interestingly, telomerase activity was induced by the expression of catalytic subunit, hTERT, in telomerase-negative normal fibroblast cells, indicating that it plays a key role in the activation of telomerase in cancer cells.
...
PMID:[Structure and regulation mechanisms of telomerase]. 961 4

Telomere shortening in human somatic cells and telomere maintenance in most human immortal cell lines and tumours correlate respectively with the absence and presence of telomerase, the enzyme that synthesizes telomeric DNA de novo . However, approximately 30% of in vitro immortalized human cell lines do not express this enzyme and maintain telomeres by an alternative pathway (ALT) that may also operate in some tumours. Human telomerase is a reverse transcriptase comprising minimally an RNA subunit (hTER) and a catalytic protein moiety (hTERT). Normal somatic cells retain expression of hTER but not of hTERT, and can be converted to a telomerase-positive phenotype by ectopic expression of the catalytic protein. We similarly have restored enzymatic activity to those ALT cell lines that retain hTER expression. We also report that in those ALT cells that are hTER negative, reintroduction of both hTER and hTERT is necessary and sufficient for conversion to telomerase positivity. Moreover, transfection of these cells with hTERT in conjunction with hTERs with a mutated template results in the expression of an enzyme with altered specificity. Reconstitution of telomerase activity in ALT cells, particularly an activity capable of synthesizing mutant telomeric DNA, may be exploited for the study of the ALT mechanism and its interaction with the telomerase-dependent pathway, and for assessing the effects of mutant telomeres on cell viability.
...
PMID:Reconstitution of wild-type or mutant telomerase activity in telomerase-negative immortal human cells. 961 72

Telomeric DNA of mammalian chromosomes consists of several kilobase-pairs of tandemly repeated sequences with a terminal 3' overhang in single-stranded form. Maintaining the integrity of these repeats is essential for cell survival; telomere attrition is associated with chromosome instability and cell senescence, whereas stabilization of telomere length correlates with the immortalization of somatic cells. Telomere elongation is carried out by telomerase, an RNA-dependent DNA polymerase which adds single-stranded TAGGGT repeats to the 3' ends of chromosomes. While proteins that associate with single-stranded telomeric repeats can influence tract lengths in yeast, equivalent factors have not yet been identified in vertebrates. Here, it is shown that the heterogeneous nuclear ribonucleoprotein A1 participates in telomere biogenesis. A mouse cell line deficient in A1 expression harbours telomeres that are shorter than those of a related cell line expressing normal levels of A1. Restoring A1 expression in A1-deficient cells increases telomere length. Telomere elongation is also observed upon introduction of exogenous UP1, the amino-terminal fragment of A1. While both A1 and UP1 bind to vertebrate single-stranded telomeric repeats directly and with specificity in vitro, only UP1 can recover telomerase activity from a cell lysate. These findings establish A1/UP1 as the first single-stranded DNA binding protein involved in mammalian telomere biogenesis and suggest possible mechanisms by which UP1 may modulate telomere length.
...
PMID:Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. 962 Jul 56

Head and neck cancer arises and progresses through specific genetic alterations which lead to an invasive immortal phenotype. The process of immortalization is associated with the activation of the enzyme telomerase, a ribonucleoprotein with reverse transcriptase activity which is capable of synthesizing telomeric repeats at the end of chromosomes. This enzyme is expressed in nearly all neoplasms and germline cells and is absent in most normal human somatic cells. Because of this expression pattern testing for telomerase activity may deliver useful diagnostic and/or prognostic information about clinical tumour behaviour. Telomerase activity was therefore analysed in 16 primary lesions of head and neck squamous cell carcinomas (HNSCC) using the polymerase chain reaction-based telomeric repeat amplification protocol (TRAP). For a sensitive semiquantitative analysis of telomerase activity TRAP products were mixed with Pico Green I and the fluorescence emission intensities were measured. All 16 samples tested positive. When the Pico Green I data were compared with clinical parameters, it was obvious that N0 necks revealed significantly (p < 0.05) lower emission intensities (i.e. telomerase activity) than N + necks. Our results indicate that a high telomerase activity in HNSCC may facilitate lymph node metastasis and that the estimation of telomerase activity is a useful diagnostic tool which could influence treatment modalities.
...
PMID:Non-radioactive semiquantitative testing for the expression levels of telomerase activity in head and neck squamous cell carcinomas may be indicative for biological tumour behaviour. 965 21

The telomere and the enzyme telomerase in esophageal cancer have been poorly investigated. We present here aspects of the telomere and telomerase in esophageal cancer in relation to cell proliferation, differentiation and chemosensitivity to anticancer drugs. The telomere length (mean length of telomere restriction fragments; TRF), telomerase activity (TA), and human telomerase RNA (hTR) expression in a panel of 13 human esophageal cancer cell lines, squamous in origin, was examined by Southern blotting, the telomeric repeat amplification protocol (TRAP), and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Cell proliferation expressed by the doubling time, cell differentiation determined by the keratin 13 and/or 14 expression, and chemosensitivity to cisplatin (CDDP) and 5-fluorouracil (5-FU) were compared with telomere-related factors. TRF shortening, the up-regulation of TA, and hTR expression was seen in all 13 cell lines. The TA correlated positively with the telomere length and negatively with the hTR expression. The doubling times of the cell lines and the telomere-related factors did not show any significant relation. The TA in the keratin 13/14-negative cell lines was significantly higher than that of the keratin 13-positive cell lines. The cells with short telomere tended to be resistant to CDDP whereas the cells with higher TA tended to be more sensitive to CDDP; 5-FU showed no relation to any telomere-related factors. Therefore, the activation of TA in esophageal squamous cell carcinoma is regulated by cell differentiation but not by cell proliferation, cells with high TA are more sensitive to CDDP, and cells with short telomere require a CDDP dose escalation.
...
PMID:Telomere length, telomerase activity and telomerase RNA expression in human esophageal cancer cells: correlation with cell proliferation, differentiation and chemosensitivity to anticancer drugs. 967 57

A contig covering the entire region of Chlorella vulgaris chromosome I (980 kb long), consisting of 33 cosmid clones has been constructed. By cross-hybridization with other chromosomal DNAs, universal structural elements were detected and localized on the contig. They were composed of at least three different elements: short interspersed DNA elements (SINE)-like elements, long interspersed DNA elements (LINE)-like elements and a putative centromere-like element. At least 36 copies of SINE-like elements were distributed over chromosome I with preferential locations on the right half of the chromosome. DNA fragments containing a SINE-like sequence showed a bent or curved DNA nature on polyacrylamide gel electrophoresis. LINE-like elements were clustered at the left terminus of chromosome I where they formed a tandem array of six copies immediately adjacent to the telomeric repeats. A long sequence element localized at a unique region of chromosome I also existed in a single copy on each chromosome and contained a sequence related to the reverse transcriptase domain of retrotransposons. This feature was compared with the reported centromere-associated elements of higher plants. With its comparative simplicity, the organization of Chlorella chromosome I genomic elements may serve as a prototypic experimental system for deciphering the complexity of huge plant chromosomes.
...
PMID:Molecular anatomy of a small chromosome in the green alga Chlorella vulgaris. 970 96

New, noninvasive methods for the early detection of urothelial carcinomas of the urinary bladder are needed for the diagnosis, follow-up, and screening of patients with bladder cancer. Detection of the enzyme telomerase in urine could offer these new diagnostic possibilities. The standard technique for detecting telomerase activity is the telomeric repeat amplification protocol (TRAP assay). Because of the instability of the ribonucleoprotein telomerase in an aggressive medium, such as urine, investigations conducted to date have yielded nonuniform or even contradictory findings. This study compares the detection of human telomerase RNA (hTR) by reverse transcriptase-PCR (RT-PCR) with detection of telomerase activity by the TRAP assay in the diagnosis of urothelial carcinoma of the urinary bladder. Sedimented cells obtained from urine of 30 patients with urothelial carcinoma, 15 patients with benign urological disorders, 3 patients as part of follow-up for malignant disease, and 20 healthy subjects were examined for the presence of hTR and for telomerase activity (TRAP). In patients with bladder cancer, telomerase activity was detected by the TRAP assay in only 2 of 30 specimens (7%). However, increased levels of hTR were detected by RT-PCR in 25 of the same 30 cases (83%). For patients with benign urological disorders, such as urolithiasis or urinary tract infections, hTR was detected in samples obtained from 4 of 15 patients (27%). Low hTR expression levels were found in 15% of the healthy controls. The detection of hTR by RT-PCR represents a promising new method for detecting malignant cells in urine.
...
PMID:Comparison of human telomerase RNA and telomerase activity in urine for diagnosis of bladder cancer. 971 24

In this study, we investigated telomerase activity and human telomerase reverse transcriptase (hTERT) mRNA expression in relation to high-risk human papillomavirus (HPV) DNA presence in the spectrum of cervical premalignant lesions. Reconstruction experiments revealed that telomerase activity determined by the telomeric repeat amplification protocol assay and hTERT mRNA by reverse transcriptase-PCR could be detected in down to 100 and 1 SiHa cervical cancer cells, respectively. Telomeric repeat amplification protocol analysis on cervical tissue specimens revealed that none of the histomorphologically normal cervical samples (n = 8) and cervical intraepithelial neoplasia (CIN) grade I (n = 10) and grade II (n = 8) lesions had detectable telomerase activity. However, telomerase activity was shown in 40% of CIN grade III lesions (n = 15) and 96% of squamous cell carcinomas (n = 24). Despite the fact that hTERT mRNA was found at much higher frequencies, semiquantitative reverse transcriptase-PCR revealed that elevated hTERT mRNA levels were strongly correlated with detectable telomerase activity. Furthermore, telomerase activity and elevated hTERT mRNA levels were only detected in cases that contained high-risk HPV DNA. In contrast, low or undetectable hTERT mRNA levels were demonstrated in both high-risk HPV positive and negative cases. These data indicate that telomerase activity detectable with the assay used and concomitant elevated levels of hTERT mRNA reflect a rather late step in the CIN to squamous cell carcinoma sequence, which follows infection with high-risk HPV.
...
PMID:Telomerase activity exclusively in cervical carcinomas and a subset of cervical intraepithelial neoplasia grade III lesions: strong association with elevated messenger RNA levels of its catalytic subunit and high-risk human papillomavirus DNA. 973 89

Zepp elements found in the telomeric region of Chlorella chromosomes show the characteristic features of non-viral (LINE-like) retrotransposons, including a poly(A) tail, 5' truncations, a retroviral reverse transcriptase-like ORF and flanking target duplications. We have isolated and characterized a full-length Zepp element (8943 bp long) from Chlorella chromosome V. Some peculiar features of this element, including nested integration, two ORF structures, a long 3' noncoding region and a possible promoter region are compared with those of the Drosophila telomeric retrotransposons HeT-A and TART. The Chlorella chromosome-Zepp system appears to represent an intermediate stage between canonical telomerase-telomeres and Drosophila retrotransposon-telomeres.
...
PMID:Structure of the Chlorella Zepp retrotransposon: nested Zepp clusters in the genome. 974 68

The reverse transcriptase telomerase is a ribonucleoprotein complex that adds telomeric repeats to chromosome ends, using a sequence within its endogenous RNA component as a template. Although templating domains of telomerase RNA have been studied in detail, little is known about the roles of the remaining residues, particularly in yeast. We examined the functions of nontemplate telomerase residues in the telomerase RNA of budding yeast Kluyveromyces lactis. Although approximately half of the RNA residues were dispensable for function, four specific regions were essential for telomerase action in vivo. We analyzed the effects of mutating these regions on in vivo function, in vitro telomerase activity, and telomerase RNP assembly. Deletion of two regions resulted in synthesis of stable RNAs that appeared unable to assemble into a stable RNP. Mutating a region near the 5' end of the RNA allowed RNP assembly but abolished enzymatic activity. Mutations in another specific small region of the RNA led to an inactive telomerase RNP with an altered RNA conformation.
...
PMID:Specific telomerase RNA residues distant from the template are essential for telomerase function. 978 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---