Replication mechanism

Although the details of the replication mechanism differ significantly between viruses, all viruses undergo the general replication steps outlined in Fig. 2. First, the... 

Naegeli H. Roadblocks and detours during DNA replication mechanisms of mutagenesis in mammalian cells. Bioessays 1994 16 557-564. 

As the field of molecular genetics grew, the DNA molecule became the focus of many research efforts. Francis Crick and George Gamov developed the sequence hypothesis to explain how DNA makes protein. They stated that the DNA sequence specifies the amino acid sequence of a protein and postulated the central dogma of molecular genetics the flow of genetic information is a one-way road, it always takes the direction from DNA to RNA to protein [16]. In the same year, 1957, Mathew Meselson and Frank Stahl demonstrated the replication mechanism of DNA [17]. In 1958, DNA polymerase became the first enzyme used to make DNA in a test tube. 

Obviously, with one single molecule no successful chemistry can be achieved (although it may he different with one DNA molecule in a living cell). In normal wet chemistry, in order to self-replicate, the replicator A must bind to another molecule A. It takes at least two molecules to make an active complex A-A, capable of starting a replication mechanism. In addition, in the case of nucleic acids one needs the four nucleotides (or whatever monomers are implied as substrates). 

So far, only the self-replication mechanisms of linear molecules have been described it is now time to consider closed spherical structures, such as micelles and vesicles. Here, the term self-reproduction will be used rather than self-replication, because, as it will be seen, the population increase is generally based on statistical processes. The subject of micelles and vesicles self-reproduction is dealt with in other chapters in this book a certain degree of repetition and/or mis-match is unavoidable. 

This is illustrated in Figure 11.3. It consists of a vesicle containing two ribozymes, one (Rib-2) capable of catalyzing the synthesis of the membrane component the other (Ribl) being an RNA replicase that is capable of repUcating itself, and reproducing the Rib-2 as well. In this way, there is a concerted shell-and-core replication, and there is therefore a basic metabolism, self-reproduction, and - since the replication mechanism is based on RNA replication - also evolvability. 

Mavelli, F. (2004). Theoretical investigations on autopoietic replication mechanisms. ETH-Z Dissertation Nr. 15218, Zurich. 

The basic DNA replication mechanism is identical for prokaryotes and eukaryotes in that an asymmetric replication fork and a RNA primer are in-... 

For the time being, therefore, the only reasonable conclusion is that a true replication mechanism appeared only at the end of precellular evolution, when the first cells came into being. Both chemical evolution and postchemical evolution, in other words, had to take place with metabolic systems that were able to tolerate errors, because only in this way could they be immune to the replication catastrophes. 

Quinolones interfere with the replication mechanism of bacteria by inhibiting essential enzymes such as DNA gyrase (topoisomerase II) and topoisomerase IV, thereby preventing supercoiling and decatenation of the bacterial DNA and the replication of the latter [5-12]. 

DNA replication, although a process that usually depends on much more sophisticated enzymic machinery [13], phenomenologically adheres to the same type of model. The various steps involved contribute to the magnitude of the overall rate, yielding under suitable reaction conditions a defined doubling time of the double-stranded molecule. Since cell division is linked with this replication mechanism, the linear autocatalytic mechanism even holds for autonomous organisms and thus found its way into population biology. 

Other non-enzyme classes of proteins include binding-proteins, antibodies, channels, pores, receptors, membrane proteins and elements of the DNA replication mechanism. Unfortunately, no 3D structure of a pharmacologically relevant membrane-bound receptor has been solved to date. 

There are still several uncertainties, even from the conceptual point of view, about the notion of self-replication. However the advantages of one such autocatalytic scheme for producing a significant concentration of active macromolecular species are commonly accepted. It is easy, at least on paper, to see how a self-replicative mechanism can give rise to the next important steps for the origin of life suppose in fact that during the self-replication cycles the compound undergoes some... 

The self-reproduction mechanism illustrated here for vesicles is of course extremely primitive with respect to the self-replication mechanisms of RNA. However, one should recognize that the first prebiotic self-replicators cannot have been chemically well-developed and sophisticated macromolecules. Most likely, the first replicators were primitive structures. In this sense, the self-reproducing supra-molecular structures have a distinct relevance, since the reproduction mechanism happens almost spontaneously. 

VVThen a beam of ionizing radiation hits living cells, important cell functions may be altered or destroyed. In particular, the replication mechanisms of the cell which are associated with their genetic material, deoxyribonucleic acid (DNA), are particularly radiosensitive. In order to appreciate fully the biological implications of this damage, further understanding at the chemical level is needed. For these reasons, we are undertaking a detailed study of the reactions of the primary reactive species in water (e aq,-OH) with nucleic acid derivatives. 

In this particular instance the drug aid inside an infected cell to get converted into a triphosphate , which is subsequently incorporated directly into DNA. In fact, this phenomenon terminates elongation of the DNA, and thereby prevents viral replication mechanism significantly. It fails to eradicate latent herpes. It is observed to be unpredictable to a certain extent as a topical prophylactic agent against particularly the recurrent infections caused by HSV-1 and HSV-2. 

DNA replication in trypanosomatids also appears to differ significandy from that in higher eukaryotes, with only one of the six subunits typically found in the eukaryotic replication origin complex being identified. There are also substantial differences in the mitochondrial replication machinety, since the complexity of the kinetoplast DNA (the trypanosomarid equivalent of a mitochondrial genome) strucmre dictates an unusual replication mechanism. "... 

An interesting question derived from these studies is why viruses utilize different strategies to modulate chemokine activity. While vCKBPs have been identified mainly in poxviruses, herpesviruses frequently encode vCKs and vCKRs. This may reflect the need to modulate different aspects of chemokine biology as a result of diverse viral replication mechanisms. 

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