Desoxyribonucleotides synthesis

NO has a cytostatic effect by inhibiting ATP synthesis [99] via Kreb s cycle (aconitase inhibition, [100]), glycolysis (GADPH inhibition) and mitochondrial respiration (NAD ubiquinone oxydoreductase and succinate ubiquinone oxydoreductase inhibitions, [101]). Another pathway is the ornithine decarboxylase inhibition. This enzyme is implicated in polyamine production necessary to cell proliferation and its activity is inhibited by NO in human colon cancer cells HT-29 and Caco-2 [102]. Furthermore NO directly inactivates ribonucleotide reductase [103] of TA3 cancer cells (murine breast cancer cells) [104]. This enzyme controlling DNA synthesis catalyses desoxyribonucleotides synthesis, and its inhibition blocks cells in S phase. This inhibition is rapid and reversible in K562 and TA3 cells [105]. 

Synthetic polymers containing either desoxyribonucleotide or ribonucleotide strands are known to stimulate the in vitro DNA synthesis by RNA tumor viruses. Some inhibitors of the DNA-polymerase reaction in RNA tumor viruses are known to exhibit a template-primer specificity6, 7 34 Table 22 shows the inhibition of template-dependent DNA polymerase activity of FLV by DEAE-F at various concentrations. The reaction catalyzed by poly (dl - dC) is most strongly stimulated by DEAE-F. Thus at 20 pg/reaction mixt. of DEAE-F the incorporation of 3H—dGMP is almost 4 times that of control. 

DNA synthesis takes place by a mechanism of complementary autoreplication. DNA is present in nearly all biological systems (with the exception of certain phages) as a double helix, formed by poly-desoxyribonucleotides, linked together by complementary hydrogen bonds between base pairs (A-T) (G-C), twisted aroxmd a common axis. Under the influence of a special enzyme, polymerase, it can unwind into single polynucleotides, each of which becomes a template for formation of the complementary chain. This process is shown diagrammatically in Fig. 1. 

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