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)

The telomerase complex and Telosome regulate, maintenance and repair telomeres. The telomerase complex is formed by complex of protein (TERT, Dyskerin, GAR, NHP2, NOP10) and nucleic acid (TERC) that together work as a reverse transcriptase. The Telosoma comprises a network of protein (TRF2, TRF1, TIN2, RAP1, TPP1 and POT1). Furthermore, dyskeratosis congenita (DC) (ORPHA1775) is a rare disease with similar characteristics to premature aging. DC is a genetically heterogeneous disease caused by mutations in the genes that encoding for different subunits of the telomerase complex and Telosome. It is known that the telomeric DNA is susceptible to oxidative stress, and telomerase activity dependent cellular redox environment. Recently a correlation between telomerase activity and catalase activity was established, and it has suggested a role of antioxidant extranuclear telomerase. However, it is not yet clear whether there is any relationship or connection between molecular telomerase activity and cellular antioxidant defense. In this paper, by using the technology of RNA interference (siRNA) silencing DKC1, NOP10 genes of telomerase complex and TINF2 of Telosoma in HeLa cells, on cellular antioxidant capacity will be presented. It was intended to see if there is a cellular effect related to the production of oxidative stress or alteration of antioxidant systems after silencing these components involved in telomere maintenance. In this paper we have evaluated the levels of DKC1, NOP10, TINF2 levels of antioxidant enzymes (CuZnSOD, MnSOD, Catalase, Gpx1, Grx1 and Trx1) by RT- qPCR and Western blotting. We analyzed the production of reactive oxygen species by fluorimetry and also assessed the activity of the telomerase complex by Sybr Green RT- QTrap.
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PMID:Characterization of the antioxidant systems in different complementation groups of Dyskeratosis Congenita. 2646 48

The telomerase ribonucleoprotein complex (RNP) is essential for genome stability and performs this role through the addition of repetitive DNA to the ends of chromosomes. The telomerase enzyme is composed of a reverse transcriptase (TERT), which utilizes a template domain in an RNA subunit (TER) to reiteratively add telomeric DNA at the ends of chromosomes. Multiple TERs have been identified in the model plant Arabidopsis thaliana. Here we combine a phylogenetic and biochemical approach to understand how the telomerase RNP has evolved in Brassicaceae, the family that includes A. thaliana. Because of the complex phylogenetic pattern of template domain loss and alteration at the previously characterized A. thaliana TER loci, TER1 and TER2, across the plant family Brassicaceae, we bred double mutants from plants with a template deletion at AtTER1 and T-DNA insertion at AtTER2. These double mutants exhibited no telomere length deficiency, a definitive indication that neither of these loci encode a functional telomerase RNA. Moreover, we determined that the telomerase components TERT, Dyskerin, and the KU heterodimer are under strong purifying selection, consistent with the idea that the TER with which they interact is also conserved. To test this hypothesis further, we analyzed the substrate specificity of telomerase from species across Brassicaceae and determined that telomerase from close relatives bind and extend substrates in a similar manner, supporting the idea that TERs in different species are highly similar to one another and are likely encoded from an orthologous locus. Lastly, TERT proteins from across Brassicaceae were able to complement loss of function tert mutants in vivo, indicating TERTs from other species have the ability to recognize the native TER of A. thaliana. Finally, we immunoprecipitated the telomerase complex and identified associated RNAs via RNA-seq. Using our evolutionary data we constrained our analyses to conserved RNAs within Brassicaceae that contained a template domain. These analyses revealed a highly expressed locus whose disruption by a T-DNA resulted in a telomeric phenotype similar to the loss of other telomerase core proteins, indicating that the RNA has an important function in telomere maintenance.
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PMID:Evolutionary and biochemical analyses reveal conservation of the Brassicaceae telomerase ribonucleoprotein complex. 3227 52