Initiation and elongation

Jenkins M, Hanley MB, Moreno MB, Wieder E, McCune JM (1998) Human immunodeficiency irus-l infection interrupts thymopoiesis and multilineage hematopoiesis in vivo. Blood 91(8) 2672-2678 Jones KA, Peterlin BM (1994) Control of RNA initiation and elongation at the HIV-1 promoter. Annu Rev Biochem 63 717-743... 

The application of forward chemical genetics to studies of translation provides an opportunity to identify small molecules that inhibit or stimulate this process without any underlying assumptions as to which step is most amenable to targeting by the chemical libraries under consideration. The opportunity exists to identify novel factors involved in translation, unravel new activities of known translation initiation factors, or characterize shortlived intermediates that are frozen by the small molecule inhibitor. We have undertaken a forward chemical genetic approach to identify small molecules that inhibit or stimulate translation in extracts prepared from Krebs-2 ascites cells (Novae et al., 2004). These screens have led to the identification of several novel inhibitors of translation initiation and elongation (Bordeleau et al., 2005, 2006 Robert et al., 2006a,b). 

H2B ubiquitination follows the early steps of transcription initiation and elongation. The E3 ligase Brel and the UBC Rad6 are recruited to the promoters that are ready to commence transcription. Initially, Brel is recruited by its interaction with transcription activators such as Gal4 in yeast or p53 in human cells. Brel in turn recruits Rad6 and its binding partner In addition to the recruitment of Rad6, H2B... 

Hsieh, C.L. (1997) Stability of patch methylation and its impact in regions of transcriptional initiation and elongation. Molecular and Cellular Biolc, 17, 5897-5904. 

Irinotecan is a topoisomerase-I inhibitory agent that prevents the initiation and elongation of RNA transcription, DNA replication, and supercoiling of DNA (44). Investi-... 

Rubber molecules are synthesized from one APP molecule, which initiates the reaction, and the rubber polymer (cw-l,4-polyisoprene) is then polymerized by sequential condensations of the non-allylic IPP (magnesium cations are a required cofactor) with release of a diphosphate at each condensation. After initiation and elongation, a termination event occurs in which the rubber molecule is released from the enzyme. Despite the similar process, remarkable differences exist between plant species with respect to enzymatic reaction mechanisms and product molecular weight. 

In view of the size of the nucleosome, it appears very difficult to carry out transcription initiation and elongation on nucleosome-covered DNA. The special role played by the nucleosome in the total transcription process is confirmed by the following experimental findings ... 

The superfamily of GTPases with their more than hundred members are divided by sequence homologies, molecular weight and subimit structure into further (super)fa-milies. These are the families of the heterotrimeric G-proteins, the Ras/GTPase superfamily and the family of initiation and elongation factors (Fig. 5.13). 

Streptolydigin inhibits both initiation and elongation. Actinomycin D, by binding to DNA, inhibits DNA polymerases as well as RNA polymerases, the... 

The second difference concerns the conformation about the thymine-deoxyribose bond of dTTP, which in the ternary complex has the configuration corresponding to a nucleotidyl unit in the product, i.e. double helical DNA. This may represent an error-preventing mechanism 338 The RNA polymerases are more complex.339 They contain two Zn2+ per molecule, although additional zinc may bind at the Mg2+ site with inhibition. There may well be multiple roles for Zn2+, both structural and catalytic. The two sites in the enzyme from B. subtilis have different340 affinities for Zn2+, in accord with this proposition. The enzyme from E. coli has at least five subunits. Zn2+ is located on the subunit which binds DNA and on the subunit on which the initiation and elongation nucleotide binding sites are located.341... 

In prokaryotic cells, with the exception of DNA primers, all types of RNA are transcribed by a single enzyme, a DNA-dependent RNA polymerase. This RNA polymerase has strict requirements for all four nucleotide-5 -triphosphates, a divalent cation, and a DNA template. Unlike DNA polymerase, there is no requirement for a primer. Initiation and elongation of RNA is in the 5 - 3 direction and the product is complementary to one of the two DNA strands, the template strand that runs in the 3 — 5 direction. The reaction may be formulated similarly to that catalyzed by DNA polymerases ... 

Yes, both bind only to the /8 subunit. But rifampicin blocks only initiation of RNA synthesis, while streptolydigin preferentially blocks elongation. This shows that the )8 subunit is involved in both initiation and elongation of RNA chains. 

The molecular mechanism of translation in eukaryotes is very similar to that in bacteria. The activation of amino acids and attachment to tRNAs and the steps of initiation, elongation, and termination of polypeptide chains are essentially the same in overall terms. The small and large ribosomal subunits of bacteria and eukaryotes are equivalent with respect to their roles in initiation and elongation of chains. 

Each of these inhibitors binds exclusively to the /3 subunit of RNA polymerase. This subunit is involved in both initiation and elongation of RNA chain growth. Rifampicin must bind to the subunit in a way that affects only the initiation step it has no effect on elongation. Streptolydigin, on the other hand, binds in a manner that blocks both activities. 

Uyama T, Kitagawa H, Tanaka J, Tamura J, Ogawa T, Sugahara K. Molecular cloning and expression of a second chon- 91. droitin A-acetylgalactosaminyltransferase involved in the initiation and elongation of chondroitin/dermatan sulfate. J. Biol. 

RNA polymerase catalyzes the initiation and elongation of RNA chains. The reaction catalyzed by this enzyme is (RNA)rt + rlbonucleoslde triphosphate (RNA)t,+, + PP ... 

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