Synthesis, cell cycle

HIV is a retrovirus in which the virus uses the body s cellular machinery to transform RNA to DNA. The number of helper T cells is dramatically reduced thereby lowering the body s immune response. GP-120 is essential to the virus binding to the cell surface receptor for entry into the cell. 14-3-3-0 is specifically implicated in the G2 checkpoint for cell cycle arrest for the HIV-1 VPR (viral protein R) accessory protein, which is associated with cell death since VPR is necessary for viral infection of helper T cells (Bolton et al. 2008). 14-3-3-0 can bind to several cyclin-dependent kinases that regulate the cell cycle leading to overall neurodegeneration in this immune disorder. Lipid peroxidation of the 14-3-3 family of proteins may cause reduced interaction with protein kinases, which can result in reduced signal transduction by which protein synthesis, cell cycle regulation, and DNA repair may be affected. 

Product formation kinetics in mammalian cells has been studied extensively for hybridomas. Most monoclonal antibodies are produced at an enhanced rate during the Gq phase of the cell cycle (8—10). A model for antibody production based on this cell cycle dependence and traditional Monod kinetics for cell growth has been proposed (11). However, it is not clear if this cell cycle dependence carries over to recombinant CHO cells. In fact it has been reported that dihydrofolate reductase, the gene for which is co-amplified with the gene for the recombinant protein in CHO cells, synthesis is associated with the S phase of the cell cycle (12). Hence it is possible that the product formation kinetics in recombinant CHO cells is different from that of hybridomas. 

Dacarbazine is activated by photodecomposition (chemical breakdown caused by radiant energy) and by enzymatic N-demethylation. Formation of a methyl carbonium ion results in methylation of DNA and RNA and inhibition of nucleic acid and protein synthesis. Cells in all phases of the cell cycle are susceptible to dacarbazine. The drug is not appreciably protein bound, and it does not enter the central nervous system. 

The eukaryotic somatic cell cycle is defined by a sequential order of tasks a dividing cell has to complete it must replicate its DNA, segregate its chromosomes, grow, and divide. The cell cycle can be divided into four discrete phases. DNA replication is restricted to S phase (DNA synthesis phase), which is preceded by a gap phase called G1 and followed by a gap phase called G2. During mitosis (M phase) the sister chromatids are segregated into two new daughter nuclei and mitosis is completed by the division of the cytoplasm termed cytokinesis (Fig. 1). 

DNA synthesis during S phase of the cell cycle resulting in a doubling of the genomic DNA. Replication can be subdivided into three distinct phases initiation, elongation, and termination. 

The phenanthroindolizidine alkaloid (-)-antofine (95) exhibits high cytotoxicity to drug-sensitive and multidrug-resistant cancer cells by arresting the G2/M phase of the cell cycle. In the first asymmetric total synthesis of (-)-95, the late-stage construction of pyrrolidine 94 for the final Pictet-Spengler cyclo-methylenation to 95 was performed by RCM and subsequent hydrogenation (Scheme 18) [67]. 

DNA Synthesis Occurs During the S Phase of the Cell Cycle... 

Othet cyclins and CDKs are involved in different aspects of cell cycle progression (Table 36-7). Cychn E and CDK2 form a complex in late Gl. Cychn E is tapidly degraded, and the released CDK2 then fotms a complex with cyclin A. This sequence is necessaty fot the initiation of DNA synthesis in S phase. A complex between cychn B and CDKl is tate-hmiting fot the G2/M transition in eukatyotic cells. 

During the S phase, mammahan cells contain greater quantities of DNA polymerase than during the nonsynthetic phases of the cell cycle. Furthermore, those eiKymes responsible for formation of the substrates for DNA synthesis—ie, deoxyribonucleoside triphosphates—are also increased in activity, and their activity will diminish following the synthetic phase until the reappearance of the signal for renewed DNA... 

In a few cases, the synthesis was directed towards well-defined oligomers (dimers, trimers, etc.). The synthesis of bis(5,7,3, 4 -tetra-0-benzyl)-EC 4/1,8-dimer from 5,7,3, 4 -tetra-0-benzyl-EC and 5,7,3, 4 -tetra-0-benzyl-4-(2-hydroxyethoxy)-EC was described by Kozikowski et al. [41]. This compound exhibited the ability to inhibit the growth of several breast cancer cell fines through the induction of cell cycle arrest in the Gq/Gi phase. Analogously, procyanidin-B3, a condensed catechin dimer, has been obtained through condensation of benzylated catechin with various 4-0-alkylated flavan-3,4-diol derivatives in the presence of a Lewis acid. This reaction led to protected procyanidin-B3 and its diastereomer. In particular, octa-O-benzylated procyanidin-B3 has been produced with high levels of stereoselectivity and in excellent isolation yields [42]. 

Figure 1. The cell cycle as a Cdc2 cycle. Progression through the eukaryotic cell cycle is sensitive to the phosphorylation state of Cdc2. A block to DNA synthesis (S) prevents dephosphorylation, and hence activation, of Cdc2. Impaired spindle function will prevent deactivation of Cdc2 and thus blocks exit from M phase (Hoyt et al., 1991 Li and Murray, 1991 reviewed in Nurse, 1991). Exit from M phase requires destruction of the regulatory subunit, Cyc B. Dephosphorylation of Cdc2 at thr-161 may act to destabilize the Cdc2/Cyc B complex and thus allow the ubiquitination of Cyc B followed by its destruction.

Eeevers I think it is more likely that there is a link between protein synthesis, growth rate and the production of a specific cell cycle regulator. This is a great mechanism to ensure a minimum cell size, making sure that cells don t divide until they are growing at a certain rate and producing everything they will need to divide at a reasonable level. 

Nasmyth The whole cell cycle can be done without protein synthesis. 

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