Ribonucleoprotein motif

Chromosome duplication in eukaryotic cells requires the enzyme telomerase which replicates the chromosome ends, the telomeres, a task that cannot be carried out by DNA replicases. (Telomerase is a ribonucleoprotein where the RNA moiety serves as template for addition of short nucleotides to the 3 end of the chromosome. The telomerase contains reverse transcriptase motifs which are essential for the duplication of the telomeres. For further information see ref. 20.). The cell-cycle clock is tightly coupled to the telomerase clock. ... 

Human telomerase is a structurally complex ribonucleoprotein that is responsible for the maintenance of telomeric DNA at the ends of chromosomes. Telomerase acts to synthesize and add a simple six-base motif (of TTAGGG in the human case) to the ends of the chromosomes, resulting in stable telomere length that would otherwise be gradually eroded after each cell replication. Active telomerase has been detected in a majority of human cancer, embryonic, and germline cells but not in normal somatic cells, with the exception of some stem cells, such as those involved in tissue renewal. 

Disruption of Necessary RNA Structure. RNA adopts a variety of three-dimensional structures induced by intramolecular hybridization, the most common of which is the stem loop. These structures play crucial roles in a variety of functions. They are used to provide additional stability for RNA and as recognition motifs for a number of proteins, nucleic acids, and ribonucleoproteins that participate in the intermediary metabolism and activities of RNA species. Thus, given the potential general activity of the mechanism, it is surprising that occupancy-based disruption RNA has not been more extensively exploited. 

The La protein is a conserved component of eukaryotic ribonucleoprotein complexes that binds the 3 poly(U)-rich elements of nascent RNA polymerase III (pol III) transcripts to assist folding and maturation. Alfano et al have determined the solution structure of N-terminal domain from La show that the La motif adopts an alpha/beta fold that comprises a winged-helix motif elaborated by the insertion of three helices. Chemical shift mapping experiments show that these insertions are involved in RNA interactions ll... 

A study of the mechanism of repair and cytotoxicity of 5-fluorouracil demonstrated that base excision repair by UNG is the major repair mechanism, but that cytotoxicity resulted primarily from its incorporation into RNA. Using CD spectroscopy, a novel major groove binding motif has been identified in which Zn(II) ions stabilise DNA containing 5-fluoro-5-Iodouracil is frequently used as a crosslinking agent, and has been used to map DNA binding sites in the Tetrahymena telomerase and in the telomerase ribonucleoprotein. ... 

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