Mammalian cell nucleus

Table 12.1. Some of the damage in a mammalian cell nucleus from 1 Gy of low-LET radiation. (Ward 1988 Goodhead 1994)...

Fakan, S., Leduc, Y., Lamarre, D., Brunet, G. and Poirier, G.G. (1988) Immunoelectron microscopical distribution of poly(ADP-ribose)polymerase in the mammalian cell nucleus. Exp. Cell Res., 179, 517-526. 

DNA occurs almost exclusively in the eukaryotic (nonbacterial, notably mammalian) cell nucleus, whereas RNA is located in the surrounding region, what is called the cytosol or cytoplasm (Voet and Voet, 1995, pp. 8, 918). The cytosolic RNA-contain-ing particles are protein rich, and are known as ribosomes. 

Within the eukaryotic cell nucleus DNA is packaged at a very high density. Textbooks now typically emphasize that for the mammalian cell nucleus this translates into 2 m of DNA contained within a roughly 10- m diameter nucleus. A better perspective is provided if we scale all dimensions by a millionfold. Now we have 2(KK) km of a 2-mm DNA fiber, which as naked DNA would behave as a stiff rod over a persistence length of roughly 5 cm ( I50 bp), within a 10-m diameter nucleus. Compaction of this DNA by chromosomal proteins yields... 

Another attribute of the NPVs is their host specificity. Viruses from the family Baculoviridae are found only in arthropods and generally possess narrow host ranges even within an insect order. Host specificity studies utilizing electron microscopy, DNA hybridization, and recombinant DNA technology have demonstrated that the baculovirus lacks the ability to transfer viral DNA into the mammalian cell nucleus even when an established cell line is used for infection (16-18), In addition, extensive studies have shown that baculovirus insecticides are safe for non-target species and the environment (19,20),... 

Phair RD, Misteli T (2000) High mobility of proteins in the mammalian cell nucleus. Nature 404 604-609... 

Ara-A is phosphorylated in mammalian cells to ara-AMP by adenosine kinase and deoxycytidine kinase. Further phosphorylation to the di- and triphosphates, ara-ADP and ara-ATP, also occurs. In HSV-1 infected cells, ara-A also is converted to ara-ATP. Levels of ara-ATP correlate directly with HSV rephcation. It has recently been suggested that ara-A also may exhibit an antiviral effect against adenovims by inhibiting polyadenylation of viral messenger RNA (mRNA), which may then inhibit the proper transport of the viral mRNA from the cell nucleus. 

Epoxides are often encountered in nature, both as intermediates in key biosynthetic pathways and as secondary metabolites. The selective epoxidation of squa-lene, resulting in 2,3-squalene oxide, for example, is the prelude to the remarkable olefin oligomerization cascade that creates the steroid nucleus [7]. Tetrahydrodiols, the ultimate products of metabolism of polycyclic aromatic hydrocarbons, bind to the nucleic acids of mammalian cells and are implicated in carcinogenesis [8], In organic synthesis, epoxides are invaluable building blocks for introduction of diverse functionality into the hydrocarbon backbone in a 1,2-fashion. It is therefore not surprising that chemistry of epoxides has received much attention [9]. 

Much of the RNA synthesized from DNA templates in eukaryotic cells, including mammalian cells, is degraded within the nucleus, and it never serves as either a strucmral or an informational entity within the cellular cytoplasm. 

In mammalian cells, the final stage of PS biosynthesis occurs in ER and MAM (Trotter and Voelker, 1994 Daum and Vance, 1997 Voelker, 2000). The other membranes in the ceU, such as mitochondria, nucleus, and plasma membrane, are therefore assembled from PS exported from ER and MAM (Figure 2). Phospholipid synthesis in mitochondria is restricted to the formation ofphosphatidylglycerol, cardiolipin, and PE, and other lipids such as PC and PS must be imported from sites of cellular lipid synthesis, ER or MAM (Daum, 1985 Vance, 1991). PS imported to the outer mitochondrial membrane is then translocated to the inner mitochondrial membrane, where it is converted to PE by PS decarboxylase (PSD) (Dennis and Kennedy, 1972 Voelker, 1990). It has been shown that the translocation of PS to mitochondria followed by its decarboxylation is a major pathway for the synthesis of PE in some cultured mammahan cells (Voelker, 1984 Kuge et al, 1986 Voelker and Frazier, 1986), suggesting that significant amounts of PE found in cell membranes are derived from mitochondria. 

Figure 2. General topological feature of PS translocation and decarboxylation in mammalian cells. PS is synthesized by PSS I and II in endoplasmic reticulum (ER) or mitochondria-associated membrane (MAM). The nascent PS is transported other membranes such as plasma membrane, nucleus, and mitochondria. The PS transported to the mitochondrial outer membrane is then translocated to the inner membrane, in which PS is converted to PE by PS decarboxylase (PSD). The PE formed in mitochondria is dynamic and can be exported to other organelles for membrane biogenesis.

If we focus on the mammalian cell, we have the plasma membrane, which encompasses the cell and separates what is inside from what is outside. We also find the membranes that isolate the nucleus, the mitochondria, the lysosomes, and other intracellular organelles from the cytoplasm. AU of these membranes have their own peculiarities and distinctions. However, it is not my purpose to make a catalog of known membrane types but to provide insights into the structural and functional features that are common to many membrane types. Since we need something specific to talk about, let s focus on the plasma membrane of mammalian cells. A schematic view of such a membrane is provided in figure 19.1. 

In mammalian cells the El ubiquitin-activating enzyme exists in two isoforms, Ela (110 kDa) and Elb (117 kDa), which are derived from a single gene and mRNA (Cook and Chock 1992, Handley Gearhart et al. 1994). The isoform Ela is predominantly found in the nucleus and has been shown to harbor a functional nuclear localization sequence (NLS) required for nuclear targeting and phosphorylation. In contrast, Elb lacks the NLS, is not phos-phorylated and localized in the cytoplasm (Handley-Gearhart et al. 1994 Stephen et al. 1997). Phosphorylation of Ela was demonstrated to occur in a cell cycle-dependent manner, being maximal in G2 phase (Stephen et al. 

In mammalian cells, previous reports proved the localization of proteasomes both in the cytoplasm and in the nucleus (Palmer et al. 1996 Peters et al. 1994). In a more recent study GFP-tagged 20 S proteasomes in fibrosarcoma cells were shown to be dispersed over the cytoplasm and nucleoplasm wherein they seem to diffuse rapidly (Reits et al. 1997). Reits et al. used a fusion protein of GFP with the proteasome subunit LMP2, ich replaces a p subimit of the proteasome upon induction with interferon y, a stimulator of... 

Neurons of the mammalian suprachiasmatic nucleus (SCN) contain cell-autonomous, self-sustained oscillators, which are able to maintain circadian periodicity even when isolated in vitro or when the animal is placed under... 

D. Ranitidine is an H2-receptor antagonist. H2-receptors are found in the cell membrane of parietal cells, not in the nucleus, nucleolus, or cytoplasm. Mammalian cells do not have cell walls. 

Figure 7.1 Drug targets at the level of cellular structure. The mammalian cell presents a variety of druggable targets. The most important ones are located at the level of the cell membrane. Within the cell, cytoplasmic organelles, such as mitochondria, are beginning to be exploited as potential drug targets. The nucleus, at the center of the cell, is an important target for the development of antineoplastic agents for the treatment of cancer.

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