Cycle, biochemical replication

Initiation is the only phase of DNA replication that is known to be regulated, and it is regulated such that replication occurs only once in each cell cycle. The mechanism of regulation is not yet well understood, but genetic and biochemical studies have provided a few insights. 

Recent laser excitation flow cytofluorometry of the dynamics of DNA metabolism in the cell cycle in zinc-deficient E. gracilis leave no doubt of the involvement of zinc in cell replication (13). The data demonstrate that all of the biochemical processes essential for cells to pass from Gi into S to G2 and from G2 to mitosis require zinc, and its deficiency can block all phases of the growth cycle of this organism. 

A unique biochemical target in the HIV-1 replication cycle was revealed when HIV protease was cloned and expressed " in Escherichia coli. HIV protease is an enzyme that cleaves gag-pro propeptides to yield active enzymes that function in the maturation and propagation of new virus. The catalytically active protca.se is a. symmetric dimer of two identical 99 amino acid subunits, each contributing the triad Asp-Thr-Gly to the active site." The homodimer is unlike monomeric asparlyl protea.ses (renin, pepsin, cathep-sin D). which also have different. substrate specificities. The designs of. some inhibitors for HIV-1 protease exploit the C2 symmetry of the enzyme. HIV-1 protease has active site speclnc ity for the triad Tyr-Phe-Pro in the unit Ser-(Thr)-Xaa-Xaa-Tyr-Phc-Pm. whenr Xaa is an arbitrary amino acid. 

Once inside the host cell, the vims must replicate its own nucleic acid. To do this, it often uses part of the normal synthesizing machinery of the host cell. If the vims is to continue its growth cycle, viral nucleic acid and viral protein must be propedy transported within the cell, assembled into the infective vims particle, and ultimately released from the cell. All of these fundamental processes involve an intimate utilization of both cellular and viral enzymes. Certain enzymes that are involved in this process are specifically supplied by the invading vims. It is this type of specificity that can provide the best basis for antiviral chemotherapy. Thus an effective antiviral agent should specifically inhibit the viral-encoded or virus-induced enzymes without inhibition of the normal enzymes involved in the biochemical process of the host cell. Virus-associated enzymes have been reviewed (2,3) (Table 1). 

Possible relations of morphological changes of cp-nucleoids in the Chlamydomonas cell cycle with such biochemical events as synthesis and replication as well as transcription of cp-DNA remains to be worked out. 

It should be noted that replication and chromosome segregation are not mutually exclusive in bacteria, especially in rapidly growing forms, where DNA synthesis and chromosome segregation may occur at the same time. Thus, when applied to prokaryotes, the term C.c.has a different meaning from that discussed above. [C.N.Norbury P. Nurse, Arm. Rev. Biochem. 61 (1992) 441-470 A.W.Murray, Nature 367 (1994) 219-220 S. Moreno P. Nurse, Nature 367 (1994) 236-242 T.W. Jacobs Cell Cycle Control Annu. Rev. Plant. Physiol. Plant Mol. Biol. 46 (1995) 317-339 A. Murray Cell 81 (1995) 149-152 J.T. Tyson et al. Trends Biochem Sci 21 (19 ) 89-96]... 

The problem is one of selectivity. Any drug must se/ecf/Ve/y kill pathogens in the presence of other living cells. Fortunately, there are sufficient biochemical differences between the metabolisms of bacterial and of mammalian cells to allow selectivity thus, safe antibiotics have been developed. Viruses present a more difficult problem because, during their replicative cycle, they become physically and functionally incorporated into host cells, and one must find biochemical features that selectively attack the virus without damaging the host. 

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