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

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

Single-molecule fluorescence spectroscopy is a powerful method to observe real time movements of individual biological molecules while they are functioning without the need for synchronization. Dynamic characteristics of nucleic acids can now be easily and reliably studied, and new applications are emerging in which their recognition and processing by proteins and enzymes are being understood with unprecedented detail. The most recent examples are discussed, including the hairpin ribozyme, Holliday junction, G-quadruplex, Rep helicase, reverse transcriptase, and combination with mechanical manipulation.
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PMID:Structural dynamics and processing of nucleic acids revealed by single-molecule spectroscopy. 1506 47

Telomeres are the physical ends of eukaryotic chromosomes. Genetic studies have established that the baker's yeast Pif1p DNA helicase is a negative regulator of telomerase, the specialized reverse transcriptase that maintains telomeric DNA, but the biochemical basis for this inhibition was unknown. Here we show that in vitro, Pif1p reduces the processivity of telomerase and releases telomerase from telomeric oligonucleotides. The released telomerase is enzymatically active because it is able to lengthen a challenger oligonucleotide. In vivo, overexpression of Pif1p reduces telomerase association with telomeres, whereas depleting cells of Pif1p increases the levels of telomere-bound Est1p, a telomerase subunit that is present on the telomere when telomerase is active. We propose that Pif1p helicase activity limits telomerase action both in vivo and in vitro by displacing active telomerase from DNA ends.
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PMID:The yeast Pif1p helicase removes telomerase from telomeric DNA. 1612 Nov 31

Telomeres, the protein-DNA complexes at the ends of eukaryotic chromosomes, are essential for chromosome stability, and their maintenance is achieved by the specialized reverse transcriptase activity of telomerase or the homologous recombination pathway in most eukaryotes. Here, we identified a human helicase, hPif1 that inhibits telomerase activity. The primary sequence and biochemical analysis suggest that hPif1 is a potential homologue of Escherichia coli RecD, an ATP-dependent 5' to 3' DNA helicase. Ectopic expression of wild-type, but not the ATPase/helicase-deficient hPif1, causes telomere shortening in HT1080 cells. hPif1 reduces telomerase processivity and unwinds DNA/RNA duplex in vitro. hPif1 preferentially binds telomeric DNA in vitro and in vivo. We propose that the mechanism of hPif1's inhibition on telomerase involves unwinding of the DNA/RNA duplex formed by telomerase RNA and telomeric DNA, and RecD homologues in eukaryotes may have evolved gaining additional functions.
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PMID:The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity. 1652 49

Telomere synthesis depends on telomerase, which contains an RNA subunit linked to a specialized reverse transcriptase subunit and several associated proteins. Here we report the characterization of four mutations in the yeast reverse transcriptase subunit Est2p that cause an overelongation of telomeres and an increase in the association of Est1p with telomeres during S phase. These 'up-mutations' are clustered in the finger subdomain of the reverse transcriptase. We show that the catalytic properties of the up-mutant telomerases are not improved in vitro. In vivo, the up-mutations neither bypass the activation step governed by Cdc13p nor do they uncouple telomerase from the Rap1p inhibition pathway. In the presence of the up-mutations, however, the ability of the Pif1p helicase to decrease telomere length and to inhibit the association of Est1p with telomeres is impaired. In addition, Pif1p associates in vivo with the telomerase RNA (TLC1) in a way that depends on the finger subdomain. We propose that, in addition to its catalytic role, the finger subdomain of Est2p facilitates the action of Pif1p at telomeres.
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PMID:The finger subdomain of yeast telomerase cooperates with Pif1p to limit telomere elongation. 1687 31

Two commercial layer chicken flocks that were fed a flax-based diet beginning at 28 weeks of age for the production of omega-3 fatty-acid-enriched eggs experienced increased mortality when the birds reached 37 weeks. The average weekly mortality was 0.34% over a 20-week period, with peak mortality of 0.9% for 1 week. Reduced feed consumption, reduced body weight gain and poor peak production were noticed prior to the onset of increased mortality. A total of 245 birds were necropsied and 78% of these had lesions in the liver and spleen, with 44% of those necropsied having changes consistent with hepatitis-splenomegaly syndrome, with lesions ranging from acute periportal lymphoplasmacytic hepatitis to chronic severe cholangiohepatitis with haemorrhage, vasculitis and amyloidosis. A total of 11% of the birds had lesions typical of fatty liver haemorrhagic syndrome, and 22% had lesions found in both hepatitis-splenomegaly syndrome and fatty liver haemorrhagic syndrome. No significant bacteria or viruses were recovered from samples of the liver/bile or spleen but 11 of 21 bile samples contained avian hepatitis E virus RNA detectable with a reverse transcriptase-polymerase chain reaction assay. Comparative sequence analysis found identities of 82 to 92% and 78 to 80% between the helicase and capsid protein genes, respectively, of the virus detected in this outbreak and those of other avian hepatitis E virus isolates, suggesting extensive genetic heterogeneity in avian hepatitis E viruses in Ontario flocks.
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PMID:Avian hepatitis E virus in an outbreak of hepatitis--splenomegaly syndrome and fatty liver haemorrhage syndrome in two flaxseed-fed layer flocks in Ontario. 1699 Jan 51

Mutations in the BRCA1-interacting DEAH helicase Brip1 confer an increased risk of breast cancer. In the present study we aimed to unravel the transcriptional control of Brip1 and to determine its expression levels in a set of 101 primary invasive breast carcinomas. Transcription of Brip1 was found to be cell growth-related and controlled by the E2F/retinoblastoma (Rb) pathway through a conserved E2F-responsive site. Repression of Brip1 expression by the cell growth-inhibiting compound 1alpha,25-dihydroxyvitamin D3 depended on this same E2F-responsive site. In spite of its role as a tumor suppressor, both quantitative reverse transcriptase-PCR analyses and immunohistochemical stainings showed significantly elevated Brip1 expression levels in grade 3 tumors as compared to grade 1 or 2 carcinomas. Furthermore, increased Brip1 transcript levels were found in tumors with an estrogen receptor-negative, progesterone receptor-negative or HER-2-positive status. In conclusion, these data show that Brip1 is a genuine target gene for the E2F/Rb pathway and that elevated expression levels of Brip1 are detected in primary invasive breast carcinomas with unfavorable characteristics.
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PMID:Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F and correlates with human breast cancer malignancy. 1834 34

Telomeres from most eukaryotes are composed of repeats of guanine-rich sequences whose main function is to preserve the end of the chromosomes. Telomeres are synthesised by a reverse transcriptase enzyme, telomerase (TERT), which forms part of a ribonucleoprotein complex containing also a RNA template molecule (TERC) and dyskerin. Exhaustion of telomeres during cell divisions triggers a DNA damage response that induces a senescence phenotype. The DNA damage machinery plays an essential role in maintaining the integrity of the genome and also detecting telomere shortening. However in some syndromes that involved mutations either in the telomerase complex genes or those involved in maintaining DNA secondary structure, such as the recQ helicase WRN, a higher frequency in the development of different types of malignancies is observed. We here describe the biology of some of these diseases, together with the molecular modifications in the telomerase complex genes and the impact of these alterations on the development of particular types of cancer.
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PMID:Telomerase deficiency and cancer susceptibility syndromes. 1991 33

HIV-1 RT (human immunodeficiency virus-1 reverse transcriptase) is a multifunctional polymerase responsible for reverse transcription of the HIV genome, including DNA replication on both RNA and DNA templates. During reverse transcription in vivo, HIV-1 RT replicates through various secondary structures on RNA and single-stranded DNA (ssDNA) templates without the need for a nucleic acid unwinding protein, such as a helicase. In order to understand the mechanism of polymerization through secondary structures, we investigated the DNA polymerization activity of HIV-1 RT on long ssDNA templates using a multiplexed single-molecule DNA flow-stretching assay. We observed that HIV-1 RT performs fast primer extension DNA synthesis on single-stranded regions of DNA (18.7 nt/s) and switches its activity to slow strand displacement synthesis at DNA hairpin locations (2.3 nt/s). Furthermore, we found that the rate of strand displacement synthesis is dependent on the GC content in hairpin stems and template stretching force. This indicates that the strand displacement synthesis occurs through a mechanism that is neither completely active nor passive: that is, the opening of the DNA hairpin is driven by a combination of free energy released during dNTP (deoxyribonucleotide triphosphate) hydrolysis and thermal fraying of base pairs. Our experimental observations provide new insight into the interchanging modes of DNA replication by HIV-1 RT on long ssDNA templates.
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PMID:Single-molecule study of DNA polymerization activity of HIV-1 reverse transcriptase on DNA templates. 1996 99

Retroviruses rely on host RNA-binding proteins to modulate various steps in their replication. Previously several animal retroviruses were determined to mediate Dhx9/RNA helicase A (RHA) interaction with a 5' terminal post-transcriptional control element (PCE) for efficient translation. Herein PCE reporter assays determined HTLV-1 and HIV-1 RU5 confer orientation-dependent PCE activity. The effect of Dhx9/RHA down-regulation and rescue with siRNA-resistant RHA on expression of HIV-1(NL4-3) provirus determined that RHA is necessary for efficient HIV-1 RNA translation and requires ATPase-dependent helicase function. Quantitative analysis determined HIV-1 RNA steady-state and cytoplasmic accumulation were not reduced; rather the translational activity of viral RNA was reduced. Western blotting determined that RHA-deficient virions assemble with Lys-tRNA synthetase, exhibit processed reverse transcriptase and contain similar level of viral RNA, but they are poorly infectious on primary lymphocytes and HeLa cells. The results demonstrate RHA is an important host factor within the virus-producer cell and within the viral particle. The identification of RHA-dependent PCE activity in cellular junD RNA and in six of seven genera of Retroviridae suggests conservation of this translational control mechanism among vertebrates, and convergent evolution of Retroviridae to utilize this host mechanism.
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PMID:RNA helicase A modulates translation of HIV-1 and infectivity of progeny virions. 2000 98

The minichromosome maintenance protein (MCM) family is involved in the regulatory role of DNA replication in eukaryotic organisms. A cDNA encoding of an MCM of the silkworm, Bombyx mori L. (Lepidoptera: Bombycidae), was cloned by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequenced. The resultant amino acid sequence and phylogenetic analysis revealed high identity to MCM, and specifically to MCM7, of vertebrates and invertebrates. An RT-PCR showed that the bmMCM7 transcript was present in the ovaries, testes, silk glands, and fat bodies of larval silkworms. Expression plasmids were transformed into competent Escherichia coli and overexpressed. This is the first report on the identification of MCM helicase of the silkworm, B. mori.
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PMID:Identification and expression analysis of minichromosome maintenance proteins in the silkworm, Bombyx mori. 2107 Jan 76


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