Transcription and Replication

Like other growth factors, the IDGFs presumably activate a signal transduction pathway that ultimately controls transcription and replication. One possibility is that they interact in some way with the insulin receptor (InsR) pathway, which has... 

Chadee DN, Allis CD, Wright JA, Davie JR (1997) Histone Hlb phosphorylation is dependent upon ongoing transcription and replication in normal and ras-transformed mouse fibroblasts. J Biol Chem 272(13) 8113-8116... 

The nucleotide components required for transcription and replication have to be imported into the nucleus from the cytoplasm, incorporation of these components into RNA leads to primary products, which are then altered by cleavage, excision of introns, and the addition of extra nucleotides (RNA maturation see p. 242). it is only once these process have been completed that the RNA molecules formed in the nucleus can be exported into the cytoplasm for protein synthesis (translation see p. 250). 

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. 

Katz, M., and F. Saibil. Herbal hepatitis Subacute hepatitis necrosis secondary to Chaparral leaf. J Clin Gastroenterol 1990 12(2) 203-206. Gnabre, ]. N., ]. N. Brady, D. J. Clanton, et al. Inhibition of human immunodeficiency virus type 1 transcription and replication by DNA sequence-selective plant lignans. Proc Natl Acad Sci 1995 92(24) 11239-11243. 

These compounds contain alkyl groups that form strong, covalent bonds with the nucleic acid bases of DNA, especially guanine. This interferes with DNA transcription and replication, inhibiting mitosis (Figure 16.1). They have a broad spectrum of antitumour activity and are used in the treatment of lymphoma, breast and ovarian carcinoma, melanoma and multiple myeloma. 

Heterologous expression systems have been of critical importance for the study of viral assembly at the molecular and structural levels. These systems afford enormous flexibility in terms of dissecting the assembly pathway and investigating protein—protein or protein—nucleic acid interactions in the absence of viral transcription and replication. In addition, moderate- to high-resolution structural analyses of assembly precursors, intermediates, and end products, all generated by expression in heterologous systems, have yielded unprecedented molecular details of the structure and function of virus particles. There can be no doubt that the application of heterologous expression systems will continue to provide answers to unresolved questions about viral assembly and structure. 

An important advantage of using heterologous expression systems is the ability to separate the assembly process from other events of the viral replication cycle such as transcription and replication, which may complicate the investigation and make interpretation of results difficult. Heterologous expression systems also allow for a more refined analysis of the assembly pathway on the basis of the possibility to express the components required for formation of the particle separately or in various combinations. As described in more detail below, this approach has been particularly useful in analyzing the assembly of large, multicomponent... 

In all cells, the DNA is supercoiled in the course of transcription and replication waves of positive and negative superturns are produced in front of and behind the ongoing polymerases, respectively (Fig. 4) [61-63]. These supertums are processed by DNA topoisomerases that prevent their accumulation and regulate the level of supercoiling. Supercoiling can be also produced by wrapping the DNA around proteins (for example in the nucleosomes), or by specific DNA topoisomerases (Fig. 4). 

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