Synthesis of DNA replication

During the Gx (first gap) phase, cells prepare to duplicate their chromosomes. 

During the S (synthesis) phase, synthesis of DNA (replication) occurs. 

During the M (mitosis) phase, cell division occurs. 

Cells may traverse the cell cycle many times. 

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Synthetic phase (S phase). Synthesis of DNA (replication) occurs and all the chromosomes in the genome are replicated during the S... 

Once the broad outlines of DNA replication and protein biosynthesis were established scien tists speculated about how these outlines af fected various origins of life scenarios A key question concerned the fact that proteins are re quired for the synthesis of DNA yet the synthesis of these proteins is coded for by DNA Which came first DNA or proteins How could DNA store genetic infor mation if there were no enzymes to catalyze the polymerization of its nucleotide components How could there be proteins if there were no DNA to code for them ... 

Nucleic acids are the last of the four major classes of biomolecules we ll consider. So much has been written and spoken about DNA in the media that the basics of DNA replication and transcription are probably known to you. Thus, we ll move fairly quickly through the fundamentals and then focus more closely on the chemical details of DNA sequencing and synthesis. 

Abstract. In eukaryotic cells, replicated DNA molecules remain physically connected from their synthesis in S phase until they are separated during anaphase. This phenomenon, called sister chromatid cohesion, is essential for the temporal separation of DNA replication and mitosis and for the equal separation of the duplicated genome. Recent work has identified a number of chromosomal proteins required for cohesion. In this review we discuss how these proteins may connect sister chromatids and how they are removed from chromosomes to allow sister chromatid separation at the onset of anaphase. 

This presented a more difficult problem How do the double-helical strands separate during DNA synthesis In a rapidly growing cell such as E. coli it has been calculated that if the strands separate by untwisting, the molecule would have to rotate at 10,000 rpm, a rate that is highly improbable. The answer to this problem lies in an understanding of the mechanism of DNA replication at the enzyme level. We will return to this subject after first considering the enzymes involved in DNA synthesis. 

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... 

Variants of histone H2A are most common in higher eukaryotes. Thus far, five H2A-type histones have been described, of which two are found in all eukaryotes from yeast to mammals (Table 1). These are the histones H2A.X, and H2A.Z (Thatcher and Gorovsky 1994). While all other eukaryotes possess a canonical H2A, S. cerevisiae utilizes H2A.X as general, replication-dependent H2A form. Vertebrates possess an additional H2A variant named macroH2A, while the fifth known H2A variant H2ABBd (Barr body-deficient), is only conserved for mammals (Chow and Brown 2003 Gautier et al. 2004). Besides the most abundant canonical H2A, which is deposited into chromatin during DNA synthesis, other H2A variants also are synthesized outside of the S phase. Like specialized variants of H3, these proteins also are available for incorporation into chromatin independent of DNA replication. 

The overall process of DNA replication requires the synthesis of both DNA and RNA. These two types of nucleic acids are synthesized by DNA polymerases and RNA polymerases, respectively. DNA synthesis and RNA synthesis are compared in Figure 1-2-2 and Table 1-2-1. 

Steinmetz KL, Spanggord RJ. 1987a. Examination of the potential of p-dichlorobenzene to induce unscheduled DNA synthesis or DNA replication in the in vivo - in vitro mouse hepatocyte DNA repair assay. 

At the cellular level, plant secondary metabolites have five major effects on herbivores (a) alteration of DNA replication, RNA transcription, and protein synthesis (b) alteration of membrane transport processes (c) enzyme inhibition and activation (d) blocking of receptor sites for endogenous chemical transmitters and (e) affecting the conformation of other macromolecules (Robinson, 1979). 

Most cytostatic agents directly or indirectly inhibit DNA replication in the S phase of the cell cycle (see p. 394). The first group (A) lead to chemical changes in cellular DNA that impede transcription and replication. A second group of cytostatic agents (B) inhibit the synthesis of DNA precursors. 

Typical classes and examples within these categories as they apply to what is currently most prescribed on the U.S. market are summarized in Table 1.8. The targets in groups 1 and 4 are unique in bacteria and absent in humans and other animals, whereas groups 2, 3, and 5 have human counterparts that are structurally different between prokaryotes and eukaryotes. These differences in targets make the use of antibiotics selective for bacteria with little or no effect on eukaryotic cells from a therapeutic perspective. However, that does not mean that antimicrobial compounds are completely inert to eukaryotes. The mechanisms that block bacterial protein synthesis, block DNA replication, and those that disrupt membrane integrity affect membrane pores. 

An enhanced understanding of protein structure, a detailed elucidation of cell replication and protein synthesis, and the isolation of DNA replication enzymes. 

How complex can the proteome of hydrogenosomes in T. vaginalis be expected to be Trichomonad hydrogenosomes have lost many standard metabolic capacities of mitochondria like—and consequently most of the proteins involved in—the tricarboxylic cycle, membrane-bound electron transport and ATP-production (Muller 1993), or fatty acid synthesis (Beach et al. 1990). Because of the absence of a genome (Clemens and Johnson 2000) the complex machineries of DNA replication and repair, gene transcription and protein synthesis are also absent from these organelles. On the other hand, experimental evidence exists for only a small number of metabolic... 

The mechanism of toxicity of ethylene glycol involves metabolism, but unlike previous examples, this does not involve metabolic activation to a reactive metabolite. Thus, ethylene glycol is metabolized by several oxidation steps eventually to yield oxalic acid (Fig. 7.84). The first step is catalyzed by the enzyme alcohol dehydrogenase, and herein lies the key to treatment of poisoning. The result of each of the metabolic steps is the production of NADH. The imbalance in the level of this in the body is adjusted by oxidation to NAD coupled to the production of lactate. There is thus an increase in the level of lactate, and lactic acidosis may result. Also, the intermediate metabolites of ethylene glycol have metabolic effects such as the inhibition of oxidative phosphorylation, glucose metabolism, Krebs cycle, protein synthesis, RNA synthesis, and DNA replication. 

Phenol was reported to induce DNA oxidative damage in human promyelocytic HL60 cells and to inhibit repair of radiation-induced chromosomal breaks in human leukocytes (Morimoto et al., 1976). However, it only slightly inhibited DNA repair synthesis and DNA replication synthesis in WI-38 human diploid fibroblasts (Poirier et al., 1975). 

Two other features deserve mention. First, there is evidence, especially in the de novo purine pathway, that the enzymes are present as large, multienzyme complexes in the cell, a recurring theme in our discussion of metabolism. Second, the cellular pools of nucleotides (other than ATP) are quite small, perhaps 1% or less of the amounts required to synthesize the cell s DNA. Therefore, cells must continue to synthesize nucleotides during nucleic acid synthesis, and in some cases nucleotide synthesis may limit the rates of DNA replication and transcription. Because of the importance of these processes in dividing cells, agents that inhibit nucleotide synthesis have become particularly important to modern medicine. 

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