DNA chains

Basically, AZT is anabohcaHy phosphorylated to AZT mono-, di-, and tri-phosphates by various enzymes (kinases) of a target ceU (159). AZT-triphosphate competes with other phosphorylated pyrimidine nucleosides for incorporation into HIV DNA by the viral reverse transcriptase. Incorporation of the AZT-triphosphate into reverse transcriptase results in viral DNA chain termination. Reverse transcriptase is essential in the repHcative cycle of HIV. 

The mode of action of PMEA may be quite similar to the mechanism by which (3)-HPMPA accomplishes its selective inhibitory activity against herpes vimses. Eor PMEA to reach its active triphosphate form, it needs only two phosphorylation steps. The triphosphate derivative of PMEA has a much stronger affinity for HIV-1 reverse transcriptase than for cellular DNA polymerases (175). Whether it is actually incorporated into DNA and terminates the growing DNA chain is currentiy under investigation. 

The antitumor antibiotic mitomycin C functions by forming cross-links in DNA chains. 

Another part of the picture in vertebrates and dowering plants is that genes are often not continuous segments of the DNA chain. Instead, a gene will begin in one small section of DNA called an exon, then be interrupted by a noncoding... 

One of the greatest scientific revolutions in history is now under way in molecular biology, as scientists are learning how to manipulate and harness the genetic machinery of organisms. None of the extraordinary advances of the past two decades would have been possible, however, were it not for the discovery in L977 of methods for sequencing immense DNA chains. 

Replication fork (Section 28.3) The point of unraveling in a DNA chain where replication occurs. 

The double helix model provides a simple explanation for cell division and reproduction. In the reproduction process, the two DNA chains unwind from each other. As this happens, a new matching chain of DNA is synthesized on each of the original ones, creating two double helices. Since the base pairs in each new double helix must match in the same way as in the original, the two new double helices must be identical to the original. Exact replication of genetic data is thereby accomplished, however complex that data may be. 

All acyclic and carbocyclic guanosine analogues depicted in Fig. 1 follow the same modus operandi as exemplified for acyclovir (ACV) in Fig. 5, in that they need three phosphorylations to be converted to their active metabolite, the triphosphate form, which then interacts with the target enzyme, the viral DNA polymerase, as a chain terminator (De Clercq 2002). In its DNA chain-terminating... 

If incorporated into me DNA chain, PMEApp and PMPApp obligatorily act as chain terminators (Fig. 6bb), following incorporation of a single molecule (PMEA... 

As has been demonstrated for tenofovir, when incorporated at the 3 -end of reverse transcriptase (RT)-driven DNA chain allows the PMPA residue to adopt multiple conformations [in contrast with the more rigid conformation of the 2, 3 -dideoxynucleosides (see infra) (Tuske et al. 2004). This greater flexibility in conformation may impede development of resistance to tenofovir. 

Nucleoside and nucleotide reverse transcriptase analogues (NRTI) lack a 3 hydroxyl group and as a result no additional nucleotides can be incorporated into the growing DNA chain. Two NRTI resistance mechanisms are identified impairment of the incorporation of the antiretroviral drug (discrimination) and removal of the analogue from the terminated DNA chain (excision) as reviewed in Chap. 3 (Arion et al. 1998 Meyer et al. 1999 Saralianos et al. 1999). 

Reverse transcriptase An enzyme coded by certain RNA vimses which is able to make complementary single-stranded DNA chains from RNA templates and then to convert these DNA chains to doublehelical form. 

Nucleoside reverse transcriptase inhibitor (NRTI)/nucleotide reverse transcriptase inhibitor (NtRI) A modified version of a naturally-occurring nucleoside or nucleotide that prevents human immunodeficiency virus (HIV) replication by interfering with the function of the viral reverse transcriptase enzyme. The nucleoside/nucleotide analog causes early termination of the proviral DNA chain. For activity, an NRTI requires three phosphorylation steps once inside the cell, whereas an NtRI has a phosphate group attached and needs only two phosphorylation steps inside the cell for activity. 

DNA polymerase I is a nonessential enzyme, since viable E. coli mutants lack it (pol A). This conclusion is complicated, however, since the enzyme catalyzes three separate chemical reactions. It polymerizes deoxyribonucleoside triphosphates, and it has two exonucleolytic activities, a 3 to 5 activity and a 5 to 3 activity. The pol A - mutants lack only the polymerization activity. Other mutants lacking both the polymerase and the 5 to 3 exonuclease activity are lethal. Thus the exonuclease function is the more important one. This fits with the role of this enzyme in removing damaged DNA segments (DNA repair) and in removing covalently attached RNA from DNA chains. We will later see that small RNAs serve as primers of DNA synthesis. 

Armin Weiss (1981) presented some results of experimental work using mont-morillonite, he was able to show that the complete information present in a matrix is passed on to the daughter layers. In principle, the intercalating synthesis of a new layer of montmorillonite from the nutrient solution can be compared to the replication of a DNA chain. The distance between the layers is of great importance in these experiments and acts as a performance-limiting factor. 

The answer is d. (Katzung, pp 831-832.) Zidovudine competitively inhibits HIV-1 nucleoside reverse transcriptase. It is also incorporated in the growing viral DNA chain to cause termination. Each action requires activation via phosphorylation of cellular enzymes. Zidovudine decreases the rate of clinical disease progression and prolongs survival in HIV-infected patients. 

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