Biosynthesis of Nucleic Acids Replication

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Before cells divide, they must synthesize a new copy of DNA. This process is called replication. 

When DNA is used as a template to synthesize RNA, the process is called transcription, and is the subject of the next chapter. 

The RNA sequence of messenger RNA is used to direct the synthesis of proteins in a process called translation. 

Naturally occurring DNA exists in many forms. Single- and double-stranded DNAs are known, and both can exist in linear and circular forms. As a result, it is difficult to generalize about all possible cases of DNA replication. Since many DNAs are double-stranded, we can present some general features of the replication of double-stranded DNA, features that apply both to hnear and to circular DNA. Most of the details of the process that we shall discuss here were first investigated in prokaryotes, particularly in the bacterium Escherichia coli. We shall use information obtained by experiments on this organism for most of our discussion of the topic. Section 10.6 will discuss differences between prokaryotic and eukaryotic replication. 

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Fig. 29. Biosynthesis of nucleic acid represented schematically according to the principle of base pairing. The threads of the double helix separate each. strand serves as template to which the complementary base components attach. The newly produced parts are shaded on the figure. After replication each double strand consists of half old and half new material ( .semiconservative... 

Nucleoprotein heteropolar complexes of nucleic acids (in particular, nuclear DNA) with basic, acid-soluble proteins (histones or protamines), and with acidic, base- or detergent-soluble non-histone chromatin proteins. N. occur mainly in the chromatin of the cell nucleus in its quiescent state, and in the chromosomes when the nucleus is active, i.e. dividing. Many viruses consist entirely of N., but N. are absent from bacteria. N. are concerned in DNA replication, and in the control of gene function during protein biosynthesis. 

The Li+-induced inhibition of the production of the HSV virus may be related to its actions upon viral DNA polymerase production and activity. Li+ reduces both the synthesis of DNA polymerase in tissue culture and the activity of DNA polymerase in vitro, each by about 50%. It has been proposed that Li+ reduces the biosynthesis of viral polypeptides and nucleic acids, and hence inhibits viral DNA replication by competition with Mg2+, a cofactor of many enzymes [243]. However, the inhibitory effect of Li+ on HSV replication in tissue culture is not affected by Mg2+ levels. A more likely hypothesis is the alteration of the intracellular K+ levels, possibly modifying levels of the high-energy phosphate compounds by replacement of either Na+ or K+ in Na+/K+-ATPase [244]. In tissue culture, HSV replication has been shown to be affected by the... 

T There are several distinct types of inhibitors of nucleotide biosynthesis, each type acting at different points in the pathways to purine or pyrimidine nucleotides. All these inhibitors are very toxic to cells, especially rapidly growing cells, such as those of tumors or bacteria, because interruption of the supply of nucleotides seriously limits the cell s capacity to synthesize the nucleic acids necessary for protein synthesis and cell replication. In some cases, the toxic effect of such inhibitors makes them useful in cancer chemotherapy or in the treatment of bacterial infections. However, some of these agents can also damage the rapidly replicating cells of the intestinal tract and bone marrow. This danger imposes limits on the doses that can be used safely. 

Base-pair hydrogen bonding of the Watson-Crick type is fundamental in all biological processes where nucleic acids are involved. These processes, which are chiefly DNA replication and protein biosynthesis [650, 651], were understood only at the molecular level when Watson and Crick discovered the three-dimensional structure of DNA [27, 527J. This structure consists of two polynucleotide chains running in opposite directions (antiparallel), and twisted into a right-handed double helix. The hydrophobic purine and pyrimidine bases are stacked in the center... 

Nucleic acids are polymers of nucleotides ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Although nucleic acids do not survive for geological periods in sediments (the maximum appears to be c.50kyr under favourable conditions) they are very important they control the self-replication of organisms (and hence provide information on evolutionary relationships) and act as the templates for protein biosynthesis. There are four nitrogen-containing bases... 

Camptothecin is currently one of the most important compounds in cancer research due to its activity against leukaemias and other cancers resistant to vincristine. Camptothecin inhibits nucleic acid biosynthesis and topoisomerase I, which is necessary for the relaxation of DNA during vital cellular processes. However, camptothecin is relatively unstable under physiological conditions prompting the preparation of more stable derivatives. Camptothecin also inhibits the replication of DNA viruses by disrupting the normal function of DNA in cellular ontogenesis. Side effects of camptothecin include haematopoietic depression, diarrhoea, alopecia, haematuria, and other urinary tract irritations. 

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